Mastitis – Patofizjologia i mechanizm

Mastitis
Patofizjologia i mechanizm

Mastitis, czyli zapalenie wymienia, to złożona choroba zapalna gruczołu mlekowego u bydła mlecznego, wywoływana głównie przez bakterie takie jak Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae oraz bakterie gram-ujemne z rodziny Enterobacteriaceae. Patogeneza obejmuje adhezję bakterii do nabłonka, inwazję, unikanie odpowiedzi immunologicznej oraz tworzenie biofilmu, co utrudnia leczenie i sprzyja przewlekłości infekcji. W odpowiedzi na infekcję dochodzi do aktywacji zarówno wrodzonego, jak i adaptacyjnego układu odpornościowego, z udziałem neutrofili, makrofagów, cytokin prozapalnych (np. IL-1, IL-6, IL-10) oraz mediatorów zapalnych, które mogą uszkadzać barierę krew-mleko i tkankę gruczołu mlekowego. Mastitis występuje w formie klinicznej (z objawami takimi jak obrzęk, zaczerwienienie, ból i gorączka) oraz podklinicznej, rozpoznawanej głównie na podstawie podwyższonej liczby komórek somatycznych (SCC) w mleku.

Patogeneza mastitis (zapalenia wymienia)

Mastitis (zapalenie wymienia) to złożona choroba zapalna gruczołu mlekowego, która może dotykać wszystkie ssaki w okresie laktacji. Schorzenie to charakteryzuje się stanem zapalnym gruczołu mlekowego i tkanek wymienia, który najczęściej jest spowodowany inwazją drobnoustrojów, choć może też wynikać z urazów mechanicznych, chemicznych lub termicznych ¹². Zapalenie wymienia stanowi jedno z najpoważniejszych wyzwań w hodowli bydła mlecznego, powodując ogromne straty ekonomiczne związane ze zmniejszoną produkcją mleka, jego gorszą jakością oraz kosztami leczenia ³.

Drogi zakażenia wymienia

Główną drogą wnikania patogenów do gruczołu mlekowego jest kanał strzykowy. Z nielicznymi wyjątkami, mastitis występuje, gdy mikroorganizmy przedostają się przez kanał strzykowy do gruczołu mlekowego ⁴. Pierwszą strukturą anatomiczną, z którą kontaktują się bakterie, jest koniec strzyku i kanał strzykowy ⁵. Zniszczenie warstwy keratynowej kanału strzykowego i rozszerzenie kanału po doju ułatwia wniknięcie mikroorganizmów do wymienia ⁶.

Zakażenie może nastąpić na dwa główne sposoby ⁷:

Przez patogeny zakaźne (kontagiozne) – obecne w zakażonych krowach, przenoszone z krowy na krowę podczas doju (głównie Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae) ⁸
Przez patogeny środowiskowe – obecne w otoczeniu krów, przenoszone ze środowiska na krowy między dojami (głównie bakterie z grupy coli, Streptococcus uberis) ⁸

W przypadku patogenów zakaźnych, transmisja następuje głównie podczas doju, poprzez ręce dojarzy lub kubki udojowe maszyny do dojenia ⁴. Wyjątkiem są bakterie Mycoplasma spp., które mogą rozprzestrzeniać się drogą aerozolową i infekować wymię po bakteriemii ⁴.

Patogeny wywołujące mastitis

Niemal każdy mikroorganizm może oportunistycznie zaatakować kanał strzykowy i wywołać mastitis. Jednak większość infekcji powodują ⁴:

Różne gatunki paciorkowców (i podobne gram-dodatnie ziarniaki)
Gronkowce (szczególnie Staphylococcus aureus)
Bakterie gram-ujemne, zwłaszcza organizmy z rodziny Enterobacteriaceae fermentujące laktozę (określane jako coliformy)
Niezakaźne Staphylococcus (NAS – non-aureus staphylococci)
Inne patogeny, takie jak grzyby, drożdże i glony (Prototheca spp.) ⁹

Staphylococcus aureus stanowi jeden z głównych patogenów powodujących mastitis u bydła, wywołując zarówno kliniczne, jak i podkliniczne zapalenie wymienia ¹⁰. Szczególnie niebezpieczne jest to, że infekcje S. aureus mogą przejść w stan chroniczny, co sprawia, że leczenie staje się bardzo trudne ¹¹.

Mechanizm zapalenia wymienia

Fazy infekcji i czynniki wirulencji

Proces patogenezy mastitis bakteryjnego można podzielić na kilka kluczowych etapów ¹²:

Adhezja – przyczepianie się bakterii do komórek nabłonkowych i macierzy pozakomórkowej, co zapobiega wypłukiwaniu ich z wymienia przez przepływ mleka. W przypadku S. aureus wykorzystywane są tu komponenty powierzchniowe rozpoznające cząsteczki adhezyjne macierzy (MSCRAMM), takie jak białko A, białka wiążące elastynę, białko wiążące kolagen, a także otoczka, peptydoglikan i kwasy tejchojowe ¹².
Inwazja – ekspresja czynników wirulencji umożliwiających wniknięcie do komórek gospodarza i tkanek. S. aureus wytwarza wtedy hemolizyny (alfa, beta, gamma, delta), leukocydynę, leukocydynę Panton-Valentine, enterotoksyny, toksyny epidermolityczne i toksynę zespołu wstrząsu toksycznego (TSST-1) ¹³.
Unikanie odpowiedzi immunologicznej – bakterie wytwarzają różne czynniki wirulencji, które pomagają im nie tylko uniknąć, ale także modulować odpowiedź immunologiczną gospodarza na ich korzyść. Czynniki te celują głównie w neutrofile i makrofagi, kluczowe komórki zaangażowane w odporność wymienia ¹³.

Istotnym elementem patogenezy jest tworzenie biofilmu, który utrudnia penetrację antybiotyków i zmniejsza skuteczność leukocytów w zwalczaniu infekcji ¹⁴. Proces tworzenia biofilmu jest związany z obecnością operonu adhezji międzykomórkowej (ica), który pośredniczy w produkcji polisacharydu/adhezyny (PS/A) i polisacharydu adhezji międzykomórkowej (PIA) ¹⁵.

U S. aureus pochodzącego od bydła występują specyficzne dla przeżuwaczy czynniki wirulencji, takie jak leukotoksyna LukMF i wariant czynnika wiążącego czynnik von Willebranda kodowany przez wyspę patogenności (SaPIvWFbp) ¹⁶. Wysoka cytotoksyczność LukMF może wynikać z wysokiej skuteczności podjednostki LukM w wiązaniu się z receptorami na leukocytach, neutrofilach i makrofagach bydlęcych ¹⁷.

Reakcja zapalna i odpowiedź immunologiczna

Gdy patogeny pokonają barierę kanału strzykowego, inicjowana jest wrodzona odpowiedź immunologiczna ¹⁸. Włącza ona zarówno obronę komórkową (neutrofile, makrofagi, komórki NK, komórki dendrytyczne, komórki nabłonka gruczołu mlekowego), jak i humoralną (układ dopełniacza, cytokiny, laktoferyna, transferyna, lizozym, białka ostrej fazy oraz reaktywne formy tlenu i peptydy przeciwdrobnoustrojowe) ¹⁸.

Proces zapalny charakteryzuje się przemieszczaniem leukocytów i białek surowicy z krwi do miejsca infekcji ³. Obecność patogenów jest wykrywana przez neutrofile, które wnikają do pęcherzyków mlecznych. Podczas tego procesu wypierają one komórki wydzielnicze, co prowadzi do zwiększenia liczby komórek somatycznych w mleku ¹⁹.

Agregacja leukocytów i czynników krzepnięcia krwi tworzy skrzepy, które utrudniają wypływ mleka z wymienia i powodują bliznowacenie oraz proliferację tkanki łącznej ¹⁹. Jeśli mikroby zostaną wyeliminowane, organizm wraca do zdrowego stanu homeostazy. Jeśli nie, aktywowany zostaje adaptacyjny układ odpornościowy, za pośrednictwem limfocytów T i B ¹⁸.

Odpowiedź immunologiczna podczas mastitis jest zróżnicowana w zależności od patogenu. Badania wykazały m.in. wyższą ekspresję genu IL-10 u krów z zapaleniem wymienia w porównaniu do zdrowych krów, co sugeruje, że zwierzęta z mastitis rozwijają preferowaną komórkową odpowiedź immunologiczną ²⁰.

Rola cytokin i mediatorów zapalnych

Odpowiedź zapalna jest kluczowym czynnikiem w procesie rozwoju mastitis. Produkcja i uwalnianie cytokin odgrywa wiodącą rolę w procesie odpowiedzi zapalnej ²¹. Zarówno ostre, jak i przewlekłe reakcje zapalne powodują uwalnianie cytokin, a ich nadmierne wydzielanie może nasilić proces zapalny i przyspieszyć rozwój choroby.

Różne czynniki endogenne lub egzogenne, takie jak inwazja bakterii, stres mechaniczny czy nowotwory, mogą aktywować wzorce molekularne związane z uszkodzeniem (DAMPs) na powierzchni błony komórkowej, np. receptory toll-podobne, lub bezpośrednio aktywować inflammasomy, takie jak NLRP3, AIM2 i NLRP1, prowadząc do uwolnienia cytokin zapalnych ²¹.

W infekcji S. aureus lipoproteiny bakteryjne mogą nasilać odpowiedź zapalną poprzez aktywację szlaków sygnałowych MAPKs i NF-κB za pośrednictwem TLR2, TLR4 i NLRP3, prowadząc do wydzielania mediatorów zapalnych, w tym PGE2, w bydlęcych makrofagach pochodnych szpiku kostnego (bBMMs) ²².

Cytokiny prozapalne uwalniane przez komórki immunologiczne mogą również niszczyć barierę krew-mleko w gruczole mlekowym. IL-6, IL-1 i inne cytokiny prozapalne mogą aktywować receptory komórek nabłonka gruczołu mlekowego, np. IL-1RI, a następnie aktywować szlak sygnałowy NF-κB, JNK i p38, powodując zapalne uszkodzenie tych komórek ²³.

Patofizjologia mastitis

Zmiany w gruczole mlekowym

Tkanka gruczołu mlekowego i przewody w całym wymieniu mogą zostać uszkodzone przez toksyny bakteryjne, co czasami prowadzi do trwałego uszkodzenia wymienia ¹. Gdy wymię zostanie zainfekowane bakteriami, uważa się, że nigdy nie staje się całkowicie wolne od organizmu ¹.

Choroba charakteryzuje się zmianami fizycznymi, chemicznymi i bakteriologicznymi w mleku oraz patologicznymi zmianami w tkance gruczołowej ²⁴. Kliniczne mastitis objawia się wyraźnymi widocznymi zewnętrznymi objawami, takimi jak obrzęk, zaczerwienienie i/lub ból wymienia, oraz ogólnoustrojową gorączką ²⁵.

Podkliniczne mastitis jest inną formą zapalenia wymienia, ale nie daje zauważalnych objawów ani oznak, takich jak zewnętrzne zmiany w wymieniu lub mleku ²⁵. Jest ono rozpoznawane głównie poprzez badanie liczby komórek somatycznych (SCC) w mleku ²⁶.

Bariera krew-mleko

Istotnym elementem patofizjologii mastitis jest naruszenie integralności bariery krew-mleko. Nieuszkodzona bariera krew-mleko nie tylko zapewnia skuteczną wymianę składników odżywczych między mlekiem a krwią, ale działa również jako bariera immunologiczna chroniąca przed inwazją patogenów ²⁷.

Badania wykazały, że S. aureus zaburza integralność bariery krew-mleko, charakteryzującą się zwiększeniem poziomu albuminy w świetle pęcherzyków, co może być markerem zwiększonej przepuszczalności tej bariery ²⁸. S. aureus obniża ekspresję białek ścisłych połączeń (TJs), w tym ZO-1, okludyny i klaudyny-3, co narusza funkcję barierową ²⁸.

Komórki nabłonka gruczołu mlekowego są ważnymi grupami komórek, które utrzymują normalną funkcję fizjologiczną gruczołu mlekowego i tworzą barierę krew-mleko. W procesie mastitis nadmierne uwalnianie cytokin poważnie niszczy te komórki ²³.

Formy mastitis i ich patofizjologia

Mastitis może występować w różnych formach, z których każda ma swoją specyficzną patofizjologię ²⁹:

Mastitis kliniczne – charakteryzuje się widocznie nieprawidłowym mlekiem (np. zmiana koloru, skrzepy fibryny) oraz objawami ogólnoustrojowymi. Prowadzi do zmniejszenia produkcji mleka.
Mastitis podkliniczne – brak widocznych objawów, ale zwiększona liczba komórek somatycznych (SCC) w mleku.
Mastitis zgorzelinowe – może wystąpić, gdy podkliniczne, przewlekłe infekcje S. aureus stają się poważne w okresach dysfunkcji immunologicznej (np. przy porodzie).

Bakterie koliformne, takie jak E. coli, często wywołują objawy kliniczne przez endotoksemię (endotoksyna uwalniana z martwych bakterii), co zwykle wiąże się z objawami ogólnoustrojowymi ¹. Z kolei infekcje bakteriami zakaźnymi wywołują odpowiedź immunologiczną (neutrofilia), z tendencją do odgradzania, prowadzącą do przewlekłej infekcji ¹.

Niektóre organizmy, np. S. aureus, wytwarzają toksyny powodujące zgorzel ⁸. Obecność specyficznych genów enterotoksyn została powiązana z ostrym i klinicznym zapaleniem wymienia u bydła ¹⁷.

Czynniki ryzyka i predyspozycje

Wiele czynników wpływa na etiologię mastitis. Ciężkość i zakres choroby zależą od równowagi między gospodarzem, gospodarstwem i patogenami ²⁵.

Czynniki związane z gospodarzem

Wysoka częstość występowania zapalenia wymienia jest silnie skorelowana z immunosupresją, której doświadczają krowy w okresie okołoporodowym ²⁵. Szczególnie wrażliwy na nowe zakażenia wewnątrzwymieniowe jest okres zasuszenia w cyklu laktacji ³⁰.

Podłoże genetyczne zwierzęcia może również determinować podatność na choroby ³¹. Badania wykazały, że bydło mleczne ze wzmocnioną i zrównoważoną odpowiedzią immunologiczną ma niższą częstość występowania chorób, w tym mastitis ³².

Główny kompleks zgodności tkankowej (MHC) odgrywa istotną rolę w indukcji i regulacji odpowiedzi immunologicznej ³². Zidentyfikowano również polimorfizmy pojedynczego nukleotydu (SNP) w innych genach kandydujących związanych z odpornością lub podatnością na mastitis ³².

Czynniki związane ze środowiskiem

Ściółka używana do hodowli bydła jest głównym źródłem patogenów środowiskowych. Jednak zanieczyszczone płyny do dippingu strzyków, infuzje wewnątrzwymieniowe, woda używana do przygotowania wymienia przed dojeniem, zbiorniki wodne lub błotniste dziury, uszkodzenia skóry, urazy strzyków i muchy były również wskazywane jako źródła infekcji ³³.

Patogeny związane z zapaleniem wymienia środowiskowym rozwijają się w warunkach wysokiej wilgotności, w gromadzącej się wodzie i gnojowicy ³⁴. Zarówno E. coli, jak i Strep. uberis mogą przetrwać miesiące w zanieczyszczonych mokrych, zabrudzonych obszarach na pastwisku ³⁴.

Stres w środowisku krów ma różnorodny wpływ na zapalenie wymienia środowiskowe ³⁵. Dlatego zmniejszenie stresu jest ważne w zapobieganiu mastitis.

Czynniki związane z zarządzaniem

Utrzymująca się obecność choroby może być przypisana złym praktykom, które obejmują niehigieniczne warunki, niewłaściwe praktyki dojenia, wadliwy sprzęt do dojenia, brak leków weterynaryjnych, złe warunki mieszkaniowe, a także strategie hodowlane nastawione na ciągłe zwiększanie wydajności mleka ²⁴.

Czynnikiem zapanym mechanicznym, wpływającym na transmisję zakażeń, może być działanie dojarki mechanicznej. Badania wykazały, że konwencjonalna dojarka może stanowić mechanizm przenoszenia bakterii wywołujących infekcje. Naprzemienne pulsacje tworzą działanie posuwisto-zwrotne w obrębie kolektora, powodując spłukiwanie mleka w kierunku strzyków, co w połączeniu ze ściskaniem gumy strzykowej stwarza działanie polegające na wypychaniu bakterii w górę kanału strzykowego ³⁶.

W przypadku patogenów zakaźnych, dorosłe krowy w laktacji są najbardziej narażone na infekcję. Głównym rezerwuarem infekcji jest gruczoł mlekowy; transmisja następuje podczas dojenia, gdy ręce dojarzy lub sprzęt do dojenia działają jako wektory ²⁹.

Znaczenie dla profilaktyki i leczenia

Zrozumienie patogenezy mastitis i jego wpływu na układ odpornościowy gospodarza jest niezwykle ważne dla opracowania skutecznych szczepionek w celu zapobiegania rozwojowi zakażeń wewnątrzwymieniowych, chorobie klinicznej oraz związanym z tym stratom produkcyjnym ¹⁰.

Strategie zapobiegania

Na podstawie wiedzy o patogenezie mastitis opracowano różne strategie zapobiegania ³⁰:

Właściwa higiena i zarządzanie dojem
Leczenie antybiotykami w okresie zasuszenia w celu zmniejszenia ryzyka nowych infekcji środowiskowych
Szczepienia przeciwko określonym patogenom mastitis
Selekcja genetyczna w kierunku wzmocnionej odpowiedzi immunologicznej (technologia HIR – High Immune Response)
Redukcja stresu w środowisku krów
Brakowanie przewlekle zakażonych krów

W przypadku patogenów zakaźnych ważne jest zapobieganie przenoszeniu bakterii między krowami podczas dojenia. Jednak w przypadku patogenów środowiskowych samo zarządzanie dojem nie wyeliminuje mastitis środowiskowego, ponieważ nie walczy z drogą od źródła środowiskowego do krowy ³⁷.

Podejścia terapeutyczne

Zrozumienie fenotypowych i genotypowych wymagań dla tworzenia biofilmu jest niezbędne do opracowania skutecznego leczenia przeciwko zapaleniu wymienia gronkowcowemu ³⁸. Białka, które zidentyfikowano jako istotne dla wirulencji, mogą stać się komponentami szczepionek zapobiegających temu bolesnemu schorzeniu ³⁹.

Opracowano różne metody leczenia mastitis, w tym ⁴⁰:

Antybiotyki (najczęściej stosowane, ale prowadzące do rozwoju wielolekoopornych bakterii)
Peptydy przeciwdrobnoustrojowe
Terapia bakteriofagowa
Probiotyki
Leczenie oparte na nanocząstkach
Tradycyjne ziołowe preparaty medyczne

Interesującym podejściem jest wykorzystanie niskocząsteczkowego białka serwatkowego (LMW-WP), które indukuje fagocytozę przez makrofagi i produkcję czynnika martwicy nowotworów (TNF-α). Aktywacja makrofagów przez LMW-WP może indukować dwa rodzaje różnicowania makrofagów: najpierw w makrofagi typu M1 w miejscu infekcji w tkance wymienia, wykazujące działanie przeciwbakteryjne, a następnie w makrofagi typu M2 o funkcjach przeciwzapalnych i immunosupresyjnych, które kończą reakcję uszkodzenia tkanki i naprawiają tkankę ⁴¹.

Nowe kierunki badawcze

Zastosowanie metod molekularnych lub opartych na DNA w badaniach i diagnostyce mastitis przyczyniło się do zwiększenia zrozumienia epidemiologii i opcji kontroli zapalenia wymienia ⁴². Dzięki wykorzystaniu narzędzi genomicznych i proteomicznych możliwe będzie dalsze badanie, jak różne subpopulacje patogenów różnią się mechanizmami powodowania chorób i transmisji ⁴³.

Bardziej zaawansowane zrozumienie patogenezy i epidemiologii bydlęcego zapalenia wymienia zapewni nowe podejścia mające na celu poprawę kontroli mastitis ⁴³. Szybkie, skuteczne i coraz bardziej opłacalne metody sekwencjonowania genomów patogenów już przyczyniły się do poszerzenia wiedzy na temat interakcji gospodarz-patogen w zapaleniu wymienia ⁴³.

Badania genetyczne i genomiczne, w tym badania asocjacyjne całego genomu (GWAS), mogą dostarczyć istotnych informacji na temat genów związanych z odpornością lub podatnością na mastitis ⁴⁴. Idealne rozwiązania mające na celu poprawę odporności na mastitis to prawdopodobnie te, które skupiają się na dużej liczbie genów, wykorzystując informacje z GWAS lub selekcję w oparciu o wartości hodowlane odpowiedzi immunologicznych ⁴⁴.

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Materiały źródłowe

#1 Bovine Mastitis mechanism pathogenesis prevention care and treatment and classification.pptx
https://www.slideshare.net/slideshow/bovine-mastitis-mechanism-pathogenesis-prevention-care-and-treatment-and-classificationpptx/266340824
Mastitis is the inflammation of the mammary gland and udder tissue in animal and it is a major endemic disease of dairy cattle. […] It usually occurs as an immune response to bacterial invasion of teat canal by variety of bacterial sources present on the farm and can also occur as a result of chemical, mechanical or thermal injury to the udder. […] Milk secreting tissues and various ducts throughout the udder can be damaged by bacterial toxins and sometimes permanent damage to the udder occurs. […] Once udder become infected with bacterial infection its said that its never become free of the organism. […] Coliforms: Clinical signs mediated through ENDOTOXAEMIA (endotoxin released from dead bacteria), hence usually associated with systemic signs. […] Contagious: Infection elicits immunological response ( PMNs), tendency of walling off leading to Chronic infection.
#2
https://link.springer.com/article/10.1007/s10911-011-9239-8
Mastitis is an inflammation of the mammary gland that is most often caused by bacterial infection and can affect all lactating mammals. […] The outcome of microbial invasion of the mammary gland depends on the complex interaction between pathogens that cause disease, the host responses that are needed to eliminate the infectious agent, and the various risk factors that will influence pathogen virulence and mammary gland defense mechanisms. […] A better understanding of important host-pathogen interactions that lead to the pathogenesis of mastitis will be needed in order to design effective mastitis control strategies. […] Mastitis can present as varying degrees of severity ranging from mild disease with no visible changes in the milk or mammary tissue to clinical disease with obvious changes to the mammary gland.
#3 Bovine Mastitis: Frontiers in Immunogenetics
https://pmc.ncbi.nlm.nih.gov/articles/PMC4188034/
Mastitis is one of the most prevalent and costly diseases in the dairy industry with losses attributable to reduced milk production, discarded milk, early culling, veterinary services, and labor costs. […] Typically, mastitis is an inflammation of the mammary gland most often, but not limited to, bacterial infection, and is characterized by the movement of leukocytes and serum proteins from the blood to the site of infection. […] It contributes to compromised milk quality and the potential spread of antimicrobial resistance if antibiotic treatment is not astutely applied. […] Despite the implementation of management practises and genetic selection approaches, bovine mastitis control continues to be inadequate. […] However, some novel genetic strategies have recently been demonstrated to reduce mastitis incidence by taking advantage of a cows natural ability to make appropriate immune responses against invading pathogens.
#4 Mastitis in Cattle – Reproductive System – Merck Veterinary Manual
https://www.merckvetmanual.com/reproductive-system/mastitis-in-large-animals/mastitis-in-cattle
With few exceptions, mastitis occurs when microbes enter the teat via the teat canal. Almost any microbe can opportunistically invade the teat canal and cause mastitis. However, most infections are caused by various species of streptococci (or similar gram-positive cocci), staphylococci, and gram-negative rods, especially lactose-fermenting organisms of enteric origin, commonly termed coliforms. […] Except for Mycoplasma spp, which may spread from cow to cow through aerosol transmission and invade the udder subsequent to bacteremia, contagious spread of pathogens occurs during milking, through such pathways as milkers hands or the liners of the milking unit. […] Most other pathogens are opportunistic invaders from the cows environment, although other streptococci and staphylococci may also have a contagious component.
#5 Mastitis: What It Is, Current Diagnostics, and the Potential of Metabolomics to Identify New Predictive Biomarkers
https://www.mdpi.com/2624-862X/3/4/50
Mastitis is a multifactorial inflammatory disease of the mammary gland. This intramammary infections (IMI) is most commonly caused by bacteria such as Escherichia coli, Staphylococcus aureus, and Streptococcus spp. and often times by fungi too. […] Mastitis-causing pathogens can be categorized into two groups: major or minor, based on their pathogenicity. The major pathogens comprise S. aureus, S. dysgalactiae, S. agalactiae, S. uberis and the Enterobacteriaceae. Cows infected with these pathogens require intensive care, and these bacteria are not easily eliminated. […] No matter the pathogen, whether it is environmental or contagious, the main route of mammary gland infection in mastitis is through the teat canal. The first anatomical structure that bacteria deal with is the teat end and teat canal.
#6 2 Immune System of Udder and Pathogenesis of Mastitis – Management of Metabolic and Production Disorders in Cattle
https://opentextbooks.colvee.org/metabolicandproductiondisorderscattle/chapter/2-immune-system-of-udder-and-pathogenesis-of-mastitis/
Historically the milk from the cows udder was thought to be sterile, but the evolution of the concept of Udder Microbiota has completely changed the thought, that the milk from the udder was sterile, because even in the normal milk, which doesn’t have any disease we could be able to isolate more than 250 strains of bacteria. […] Among these Microbiota some are pathogenic, which may be harmful to the udder and others are actually beneficial, which may prevent the occurrence of Mastitis. […] So having all these immune systems how a pathogen causes Mastitis, prepare loss of keratin layer and post milking dilatation of the teat canal, this facilitates the entry of microorganism into the udder. […] So once the organisms enter into the udder, they are being facilitated by the udder environment. Even they get horizontal signaling from the udder microbiota which is already residing in the udder.
#7 (PDF) Etiology, Pathogenesis, Risk Factors, Diagnosis and Management of Bovine Mastitis: A Comprehensive Review
https://www.academia.edu/42349583/Etiology_Pathogenesis_Risk_Factors_Diagnosis_and_Management_of_Bovine_Mastitis_A_Comprehensive_Review
Mastitis, an inflammation of mammary gland, is the most devastating disease of dairy animals because of huge economic losses. […] The main transmission route through which these pathogens get access to the mammary gland, is the teat canal. […] Based on the direction of transmission of these causative agents, mastitis can be viewed from two major angles: contagious and environmental mastitis. […] Epidemiological factors including host factors, agent factors and managemental factors contribute for the occurrence of the disease. […] Mastitis is characterized by the presence of one or more of symptoms, such as abnormal milk color, presence of clots in milk, udder swelling, pain, and systemic signs including elevated temperature, lethargy, and anorexia. […] Major pathogens most often cause clinical mastitis, and give rise to the most extensive changes of milk composition.
#8 Bovine Mastitis mechanism pathogenesis prevention care and treatment and classification.pptx
https://www.slideshare.net/slideshow/bovine-mastitis-mechanism-pathogenesis-prevention-care-and-treatment-and-classificationpptx/266340824
Some organisms e.g. S.aureus produce toxin gangrene. […] Contagious bacteria (S. aureus, S.agalactiae, S.dysgalactiae) present in infected cows, therefore mastitis is transmitted from COW to COW during milking. […] Environmental bacteria (Coliforms, S. uberis) present in the Environment, therefore mastitis is transmitted from ENVIRONMENT to COWS between milkings. […] Mastitis can be identified by abnormalities in milk like clots or a watery appearance, or signs of swelling, heat, redness, and hardness in the udder. […] Proper hygiene, treatment with antibiotics, and culling of chronically infected cows can help control mastitis.
#9 Animals | Special Issue : Mastitis in Farm Animals: Pathogenesis, Diagnosis, Control, and Prevention
https://www.mdpi.com/journal/animals/special_issues/HW9076M470
Mastitis is an infection of mammary glands with pathogenic or opportunistic microorganisms (bacteria, fungi, yeast, and algae) that results in inflammation and loss or reduction in milk production. […] One of the major bottlenecks for the development of effective and sustainable control tools is a limited understanding of the pathogenesis of intramammary infections and host immunological defenses or other therapies required to cure each pathogen. […] This Special Issue aims to compile the latest and most advanced technology-supported concise summary of the pathogenesis and effective and sustainable control and prevention tools for mastitis. […] Research areas may include (but are not limited to) the following: Pathogenesis of mastitis; Hostâpathogen interactions; Host immunological responses during mastitis; Host transcriptomic, proteomic, and metabolomic responses during mastitis.
#10 Pathogenesis, Diagnosis, Control, and Prevention of Bovine Staphylococcal Mastitis | IntechOpen
https://www.intechopen.com/chapters/79882
Bovine mastitis is the single most costly disease usually caused by Bacteria. The genus Staphylococcus is major bacteria that cause mastitis in dairy cattle. Staphylococci that cause bovine mastitis are commonly divided into two major groups such as 1) Staphylococcus aureus and 2) non-aureus staphylococci (NAS). Staphylococcus aureus causes clinical and subclinical mastitis in dairy cows. […] To develop an innovative control tool detailed understanding of staphylococcal virulence factors, pathogenesis, and host immunological responses is critically important. This chapter discusses the pathogenesis, host responses and current control and prevention methods. […] Detailed understanding of staphylococcal virulence factors and pathogenesis of staphylococcal intramammary infections (IMI) in the dairy cow is necessary to develop an effective vaccine. Understanding the pathogenesis of staphylococcal mastitis and its effects on the host immune system is critically important to develop effective vaccines to prevent the establishment of IMI, clinical disease, and subsequent production losses.
#11 Diversity and pathogenesis of Staphylococcus aureus from bovine mastitis: current understanding and future perspectives | BMC Veterinary Research | Full Text
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-022-03197-5
Toxins such as alpha and beta hemolysins promote necrosis of the mammary gland tissue and lyse bovine erythrocytes to use hemoglobin as a source of iron. […] The high prevalence reported for the fnbA gene in bovine isolates may reflect the importance of this adhesin in the pathogenesis of bovine mastitis. […] In summary, the expression of a large array of surface proteins with the ability to bind to extracellular matrix proteins by bovine S. aureus highlights the different strategies that have evolved to promote colonization and pathogenesis. […] Current evidence indicates the involvement of SAgs in the pathogenesis of bovine mastitis. […] These findings show that although biofilm production is usually described as a primordial factor that contributes to persistence other bacterial traits may also support chronic infections during bovine mastitis.
#12 Mastitis in Small Ruminants | IntechOpen
https://www.intechopen.com/chapters/76529
The pathogenesis of S. aureus mastitis is very complex. It is associated with various surface proteins and virulence factors that are differentially expressed at various phases of the infection. This process entails three key steps, that is adhesion, invasion and evasion. […] The first step in the pathogenesis process is adhesion to epithelial cells and extracellular matrix, which permits the bacteria to avoid being flushed out of the udder from milk flux pressure. […] During this step S. aureus expresses several virulent factors involved in adhesion, such as Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMM), e.g. protein A, elastin-binding proteins, collagen-binding protein etc.; surface-associated capsule (which inhibits phagocytosis and promotes adhesion); peptidoglycan (which activates complement); teichoic acids (involved in adhesion and colonization, cell division and biofilm formation).
#13 Mastitis in Small Ruminants | IntechOpen
https://www.intechopen.com/chapters/76529
In the second step of this process, S. aureus again expresses different virulence factors to establish infection by invasion into host cells and tissues. This step or phase entails penetration and destruction of mammary glands tissues by the bacteria and involves the expression of the following virulence factors: haemolysins (i.e., alpha, beta, gamma delta, these lyse cells); leukocidin (damages polymorphonuclear leucocytes); panton-valentine leukocidin (a -pore-forming toxins); enterotoxins (heat stable toxin); epidermolytic toxin (this is a serine protease that causes splitting of desmosomes or intercellular bridges in the stratum granulosum); toxic shock syndrome toxin (TSST-1, causes leakage of endothelial cells and penetration of mucosal barrier). […] The final step in the pathogenetic process is an evasion of the host immune response. Here, S. aureus escapes the host immune response by producing the various virulence factors that helps it not only to evade but also modulate the host immune response in its favor. […] S. aureus virulence factors target the main cells involved in mammary immunity, such as neutrophils and macrophages.
#14 Pharmacological activity of South African medicinal plants and mechanism of action against Staphylococcus aureus isolated from clinical bovine mastitis
https://repository.up.ac.za/handle/2263/98440
Bovine mastitis infection is mostly caused by Staphylococcus and Streptococcus species and has gained global importance due to the increase of multi-drug resistant bacteria, and resistance to common antibiotic therapy. […] Most staphylococci associated with bovine mastitis can express biofilm which can prevent and reduce the effects of antibacterial agents and the efficacy of the leucocytes. […] Some mastitis pathogens developed resistance to antimicrobials due to their ability to form biofilm and spread this characteristic through the processes of transformation, conjugation and transduction. […] Gene replication during biofilm formation can lead to mutation (remodeling of the gene), and bacteria during this process protect themselves by producing extracellular polymeric substances leading to antibiotic resistance.
#15 Pathogenesis, Diagnosis, Control, and Prevention of Bovine Staphylococcal Mastitis | IntechOpen
https://www.intechopen.com/chapters/79882
The severity and duration of staphylococcal mastitis are partially due to the wide range of bacterial virulence factors. These virulence factors are produced at differing quantities depending on the stage of infection and host immune response. […] Staphylococcal virulence factors can be divided into intrinsic and acquired classes. […] A multitude of factors attributes to the ability of staphylococcal bacterial virulence and antibiotic resistance. […] The initial attachment of the biofilm complex is via a capsular antigen: polysaccharide/adhesin (PS/A). […] The formation of different biofilms has also been associated with additional slime production, thought to increase bacterial adhesion and colonization. […] The production of PIA and PS/A in staphylococcal species is mediated by the intercellular adhesion operon (ica).
#16 Genomic analysis of European bovine Staphylococcus aureus from clinical versus subclinical mastitis | Scientific Reports
https://www.nature.com/articles/s41598-020-75179-2
Some of these immune evasion factors are considered ruminant adapted, such as LukMF and the S. aureus pathogenicity island encoded variant of the Von Willebrand factor-binding protein (SaPIvWFbp). […] The majority of virulence and AMR genes are located on mobile genetic elements and S. aureus belonging to the same CC have specific virulence gene signatures due to clonal expansion and restriction-modification systems that reduce HGT between different S. aureus lineages. […] A key finding of the current study was the association between S. aureus belonging to CC479 and CM. […] The underlying mechanisms for this apparent increased virulence of CC479 remains unknown, but we have suggested a SNP in the repressor of toxins (rot) gene, resulting in an increased production of LukMF by CC479 isolates as a possible cause.
#17 Diversity and pathogenesis of Staphylococcus aureus from bovine mastitis: current understanding and future perspectives | BMC Veterinary Research | Full Text
https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-022-03197-5
Taken together, these studies reveal the importance of Hla and Hlb in bacterial virulence during IMI. […] The presence of specific enterotoxin genes has been linked to acute and clinical bovine mastitis. […] The high cytotoxicity of LukMF may be conferred by the high efficiency of LukM for cell receptors present on bovine leukocytes, neutrophils, and macrophages. […] Taken together, these studies strongly support the functional significance of LukMF in the pathogenesis of bovine mastitis.
#18 Mastitis: What It Is, Current Diagnostics, and the Potential of Metabolomics to Identify New Predictive Biomarkers
https://www.mdpi.com/2624-862X/3/4/50
When mastitis-causing pathogens pass this barrier, an innate immune response (IIR) is initiated. […] This immune response is mediated at the beginning by innate immunity. It includes both cellular (e.g., polymorphonuclear neutrophils (PMN), macrophages, natural killer (NK) cells, dendritic cells, mammary epithelial cells (MEC), and humoral defenses (complement system, cytokines, lactoferrin, transferrin, lysozyme, acute phase proteins (APPs) as well as reactive oxygen species (ROS) and antimicrobial peptides. […] If microbes are eliminated, the host returns to a healthy, homeostatic state. If not, the adaptive immune system is activated. This response is mediated by T and B lymphocytes. […] Depending on the type and scale of pathogen invasion, this infection is presented either in a clinical or subclinical form.
#19 2 Immune System of Udder and Pathogenesis of Mastitis – Management of Metabolic and Production Disorders in Cattle
https://opentextbooks.colvee.org/metabolicandproductiondisorderscattle/chapter/2-immune-system-of-udder-and-pathogenesis-of-mastitis/
Next, some of the bacteria like staphylococcus aureus and even E-coli go for Biofilm formation and Internalization. […] So during this process even if the macrophages engulf, they go for encapsulation and remain dormant and live in the macrophages and also release proteases and toxins like alpha and beta, which on one side destroy the antibodies and on the other side they damage the epithelial cells and get internalized into the epithelium, where they reside for a long time with low activity and they again cause chronic Mastitis in due course of time. […] On the other side, the presence of pathogens is sensitized by the neutrophils and they enter into alveoli, while entering into the alveoli, they displace the secretory cells leading to increased somatic cell count in the milk. […] Aggregation of these leukocytes and blood clotting factors forms clots, which abstract the flow of milk out of the udder and they also cause scar formation and proliferation of connective tissue.
#20 SciELO Brazil – Expression profile of genes associated with mastitis in dairy cattle Expression profile of genes associated with mastitis in dairy cattle
https://www.scielo.br/j/gmb/a/RqGz4dTkR79r37jCFjKB9Yx/
In order to characterize the expression of genes associated with immune response mechanisms to mastitis, we quantified the relative expression of the IL-2, IL-4, IL-6, IL-8, IL-10, IFN- and TNF- genes in milk cells of healthy cows and cows with clinical mastitis. […] These findings suggest that animals with mastitis develop a preferentially cell-mediated immune response. […] The present results agree with the findings of Riollet et al. (2001) who observed a higher expression of IL-10 in milk cells of animals with chronic mastitis caused by Staphylococcus aureus compared to healthy cows. […] These results suggest a higher expression of the IL-10 gene in BW Holstein cows with mastitis when compared to Gyr cows with mastitis. […] These findings suggest that animals with mastitis develop a preferentially cell-mediated immune response.
#21 The Mechanism of Metabolic Immune Microenvironment, Inflammation and Blood Milk Barrier in Mastitis | Frontiers Research Topic
https://www.frontiersin.org/research-topics/25150/the-mechanism-of-metabolic-immune-microenvironment-inflammation-and-blood-milk-barrier-in-mastitis/magazine
Inflammatory response is an important driving factor in the occurrence and development of mastitis. The production and release of cytokines plays a leading role in the process of inflammatory response. Both acute and chronic inflammatory reactions will cause the release of cytokines, and the excessive release of cytokines will aggravate the inflammatory process and accelerate the disease process. […] During the occurrence and development of mastitis, the production and release of cytokines, the integrity of blood milk barrier and the disease process of mastitis are closely related. Mastitis is mainly caused by various endogenous or exogenous factors, such as bacterial invasion, tumor, mechanical stress and so on. Various endogenous or exogenous factors can activate damage-associated molecular pattern (DAMPs) on cell membrane surface, such as toll like receptors, or directly activate inflammasomes such as NLRP3, AIM2 and NLRP1, resulting in the release of inflammatory cytokines. Inflammatory cytokines recruit immune cells from all over the body to enter the mammary gland, and the immune cells gathered in the mammary gland will continue to release a large amount of inflammatory cytokines after receiving stimulation.
#22
https://figshare.com/articles/dataset/An_underlying_mechanism_of_bovine_mastitis_PGE_sub_2_sub_regulates_i_Staphylococcus_aureus_i_-induced_inflammatory_response_through_TLR2_TLR4_and_NLRP3_in_macrophages/28768157
Staphylococcus aureus (S. aureus) evades the immune system by altering macrophage functions, including immune regulation and phagocytosis, leading to the development of bovine mastitis. […] The results showed that during bovine mastitis, the macrophages are recruited into the mammary gland, accompanied by a significant upregulation of inflammatory mediators in the mammary tissue. […] Furthermore, S. aureus lipoproteins could increase the inflammatory response by mediating MAPKs and NF-B signaling pathway activation through TLR2, TLR4, and NLRP3, leading to the secretion of inflammatory mediators, including PGE2, in bovine bone marrow-derived macrophages (bBMMs). […] The bBMMs were treated with TLR2, TLR4, and NLRP3 inhibitors, which can decrease the expression of COX-2 and mPGES-1, further regulating PGE2 synthesis and secretion in S. aureus infection.
#23 The Mechanism of Metabolic Immune Microenvironment, Inflammation and Blood Milk Barrier in Mastitis | Frontiers Research Topic
https://www.frontiersin.org/research-topics/25150/the-mechanism-of-metabolic-immune-microenvironment-inflammation-and-blood-milk-barrier-in-mastitis/magazine
The immune cells over activated by inflammatory cytokines may mediate cell death, apoptosis or necrosis through caspase-3, caspase-1 and other pathways. Dead immune cells will lead to the uncontrolled release of cytokines into the mammary microenvironment, which will mediate mammary injury, and even cause cytokine storm, which is life-threatening. The pro-inflammatory cytokines released by immune cells will not only affect the immune cells themselves, but also further destroy the blood milk barrier in the mammary gland. […] Mammary epithelial cells are important cell groups that maintain the normal physiological function of mammary gland and form the blood milk barrier. In the process of mastitis, the excessive release of cytokines will seriously destroy mammary epithelial cells. IL-6, IL-1 and other pro-inflammatory cytokines can activate the receptors of mammary epithelial cells, such as IL-1RI, and then activate the NF-?B, JNK and p38 signal pathway, resulting in inflammatory damage of mammary epithelial cells.
#24 (PDF) Etiology, Pathogenesis, Risk Factors, Diagnosis and Management of Bovine Mastitis: A Comprehensive Review
https://www.academia.edu/42349583/Etiology_Pathogenesis_Risk_Factors_Diagnosis_and_Management_of_Bovine_Mastitis_A_Comprehensive_Review
The disease is characterized by physical, chemical and bacteriological changes in the milk and pathological changes in the glandular tissue of the udder. […] Infectious agents, in particular, the various species of bacteria are accounted as the most important etiologic agents of mastitis. […] The disease is characterized by physical, chemical and bacteriological changes in the milk and pathological changes in the glandular tissues. […] The continuing presence of the disease may be attributed to poor practices which includes unhygienic conditions, improper milking practices, faulty milking equipment, lack of veterinary medicines, poor housing besides breeding strategies for ever-increasing milk yield. […] The incidence of disease is thus result of interplay between the infectious agents and management practices emphasizing the importance of udder defense.
#25 Mastitis: What It Is, Current Diagnostics, and the Potential of Metabolomics to Identify New Predictive Biomarkers
https://www.mdpi.com/2624-862X/3/4/50
Clinical mastitis manifests with clear visible external signs such as swelling, redness and/or pain in the udder, and systemic fever. […] Subclinical mastitis is another form of mastitis but does not present with any noticeable symptoms or signs such as external changes in the udder or milk. […] Many factors participate in the etiology of mastitis. Disease severity and extent depend on the balance between the host, the farm, and the pathogens. […] A high incidence of IMI is strongly correlated with the immunosuppression that cows go through around parturition. […] The origin of these pathogens can be from the environment, the udder, or an existing infection. […] It has been demonstrated that mastitis-positive cows identified within 30-100 days in lactation likely had the infection since the dry period.
#26 Mastitis: What It Is, Current Diagnostics, and the Potential of Metabolomics to Identify New Predictive Biomarkers
https://www.mdpi.com/2624-862X/3/4/50
The inflammatory response seen in a cow’s udder can indicate the presence of mastitis, whereas the identification of the bacterial pathogen causing the disease confirms the intramammary infection. […] The somatic cell count or SCC indicates an IMI and gives an overview of a cow’s udder health. […] The somatic cell count (SCC) is a traditional approach to diagnose mastitis.
#27 Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity | PLOS Pathogens
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011764
The well-known metabolites include microbiota-derived short-chain fatty acids (SCFAs), tryptophan-derived ligands of aryl hydrocarbon receptor (AhR), and bile acids, which have been reported to participate in multiple diseases. […] HEX was found to alleviate S. aureus-caused mastitis by depressing inflammatory response and maintaining blood-milk barrier integrity. […] The underlying mechanism was involved in peroxisome proliferator-activated receptor- (PPAR)-mediated the activation of sirtuin1 (SIRT1), which blocked NF-B pathway activation caused by S. aureus. […] HEX also ameliorated mammary and colonic inflammation and barrier injury caused by S-RMT. […] Collectively, HEX is a potential prophylactic agent for SARA- and S. aureus-induced mastitis in mice. […] The undamaged blood-milk barrier not only ensures effective nutrient exchange between milk and blood, but also acts as an immune barrier to resist the invasion of pathogens.
#28 Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity | PLOS Pathogens
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1011764
Consistent with the findings of previous studies, S. aureus was found to disrupt the integrity of the blood-milk barrier characterized by increasing albumin in the acinar lumen, which might be a marker of increased blood-milk barrier permeability. […] Interestingly, HEX pretreatment recovered the barrier function and improved mastitis. […] Here, we found that S. aureus downregulated the expression levels of TJs, including ZO-1, Occludin, and Claudin-3; however, HEX reversed these changes, thereby demonstrating its protective role in barrier functions. […] Collectively, HEX alleviated inflammatory response via PPAR-SIRT1-NF-B axis in vitro and HEX also rescued S. aureus-induced mastitis in a dose-dependent manner in vivo.
#29 Mastitis in Cattle – Reproductive System – Merck Veterinary Manual
https://www.merckvetmanual.com/reproductive-system/mastitis-in-large-animals/mastitis-in-cattle
Milk production decreases in cows with subclinical mastitis. The loss of milk from inflammation is directly proportional to the individual cow SCC; as SCC rises, milk production decreases. […] Clinical mastitis is an inflammatory response to infection causing visibly abnormal milk (eg, color, fibrin clots). […] Gangrenous mastitis can also occur, particularly when subclinical, chronic infections of S aureus become severe at times of immune dysfunction (eg, at parturition). […] For contagious pathogens, adult lactating cattle are most at risk of infection. The primary reservoir of infection is the mammary gland; transmission occurs at milking with either milkers hands or milking equipment acting as fomites. […] For Streptococcus agalactiae, Staphylococcus aureus, and nonaureus staphylococci, there is little or no seasonal variation in the incidence of infection.
#30 Mastitis in Cattle – Reproductive System – Merck Veterinary Manual
https://www.merckvetmanual.com/reproductive-system/mastitis-in-large-animals/mastitis-in-cattle
The most important measure to monitor subclinical mastitis in dairy herds is testing milk for SCCs and the calculation of key performance indicators. […] Subclinical mastitis treatment is indicated when treatment costs are expected to be outweighed by production gains after elimination of infection. […] However, prevention is always preferred to treatment, particularly because lactating glands have compromised immune function and are therefore susceptible to infection. […] The dry period of the lactation cycle is a critical time for the udder health of dairy cows. […] During this time, the gland is particularly vulnerable to new intramammary infections. […] The primary causative agent of protothecal mastitis in cattle has been identified as Prototheca zopfii. […] Mastitis caused by Prototheca spp are managed in similar fashion, regardless of species or genotype.
#31
https://link.springer.com/article/10.1007/s10911-011-9239-8
Inflammation of the mammary gland is an important host response to invading pathogens, but escalation of antimicrobial defenses can have a detrimental impact on host tissue and can disrupt and impair mammary gland function. […] The review by Aitken, Corl and Sordillo explores in detail the current knowledge of critical host-pathogen interactions that occur during mastitis that can either result in the elimination of invading pathogens and restoration of immune homeostasis or lead to uncontrolled inflammatory responses that can disrupt normal mammary gland function. […] The genetic background of an animal also can dictate disease susceptibility. […] This special issue on the causes and control of mastitis provides a compilation of in-depth reviews that emphasize the complex interaction between the immunological defenses of the mammary gland, diversity of microorganisms that cause infection, and the environment of both the host and pathogens that contribute to mastitis.
#32 Bovine Mastitis: Frontiers in Immunogenetics
https://pmc.ncbi.nlm.nih.gov/articles/PMC4188034/
Both innate and adaptive host defenses are required to protect the host from infection. […] The ideal immune response being one that appropriately recognizes epitopes on the invading pathogen to initiate swift and accurate clearance mechanisms while maintaining minimal pathological consequences. […] In fact, dairy cows classified as high responders (robust and balanced responses) for adaptive immune response traits have been demonstrated to have reduced disease incidence. […] The major histocompatability complex (MHC) plays an essential role in the induction and regulation of immune responses. […] Genetic variation, such as single nucleotide polymorphisms (SNP) in other candidate genes associated with resistance or susceptibility to mastitis have been identified. […] Recent studies are beginning to uncover information about the epigenetic influences on bovine immune response genes.
#33 Mastitis in Cattle – Reproductive System – Merck Veterinary Manual
https://www.merckvetmanual.com/reproductive-system/mastitis-in-large-animals/mastitis-in-cattle
In addition, contagious transmission may infrequently occur for pathogens typically associated with environmental reservoirs, either through the development of host-adapted virulence factors (as for Escherichia coli) or by shedding of overwhelming numbers of bacteria from infected udders (as for Trueperella [formerly Arcanobacterium] pyogenes and Lactococcus spp). […] The bedding used to house cattle is the primary source of environmental pathogens; however, contaminated teat dips, intramammary infusions, water used for udder preparation before milking, water ponds or mud holes, skin lesions, teat trauma, and flies have all been incriminated as sources of infection. […] Detection of subclinical mastitis is best done by testing milk for somatic cell counts (SCCs; predominantly leukocytes) using either the California Mastitis Test or automated methods provided by dairy herd improvement organizations.
#34 Mastitis Part 10 – Environmental Mastitis
https://www.nadis.org.uk/disease-a-z/cattle/mastitis/mastitis-part-10-environmental-mastitis/
Both E. coli and Strep uberis, particularly the latter, can also cause environmental mastitis in cows on pasture as they can survive for months in contaminated wet soiled areas. […] Infections can occur during the dry period or can be picked up during lactation. […] A crucial time for infection with new environmental mastitis-causing bacteria is the dry period or around calving. […] In order to control environmental mastitis, we have to focus on environmental management throughout the cow’s lactation cycle as well as the non lactation period. […] Pathogens associated with environmental mastitis thrive in high humidity conditions, in pooling water and slurry. […] Dry cow therapy will reduce the risk of new environmental infections, particularly in cows with a history of mastitis or high cell counts.
#35 Mastitis Part 10 – Environmental Mastitis
https://www.nadis.org.uk/disease-a-z/cattle/mastitis/mastitis-part-10-environmental-mastitis/
There are now multiple options for cattle vaccination against specific mastitis pathogens available in the UK, and are a suitable consideration for mastitis control and increasing immunity for some herds. […] Although environmental bacteria spread outside the parlour, good milking management will help to reduce environmental mastitis. […] Reducing stress in a cows environment has a variety of beneficial impacts on environmental mastitis. […] Ensuring good immunity both at the level of the udder and systemically is important in helping cows to fight infection in the udder. […] Proper mastitis records with good bacteriology are essential to tackling an environmental mastitis problem.
#36 Mastitis: The milking machine as the delivery mechanism – | Ag Proud
https://www.agproud.com/articles/21064-mastitis-the-milking-machine-as-the-delivery-mechanism
Forbes determined that non-motile bacteria, such as Staph. aureus, are forced up the teat canal during the milking process by the pinching action of the liner. […] The evidence and data leads to the conclusion that the pinching of the liner on the teat end will forcibly shove the keratin lining of the teat canal carrying the bacteria up into the sinus to cause an IMI. […] The fact that the industry still suffers the serious financial impact of mastitis after decades of research and focus on cleanliness and management is proof that another mechanism of infection exists. […] The research by Forbes and others strongly suggests that the conventional milking machine is the delivery mechanism for bacteria causing the infections. […] Alternating pulsation creates a back-and-forth pushing action within the claw causing milk to be washed up against the teats and is combined with the liner pinching, creating the action to drive the bacteria up the teat canal, effectively making the milking machine the delivery mechanism for new infections.
#37 Mastitis Part 10 – Environmental Mastitis
https://www.nadis.org.uk/disease-a-z/cattle/mastitis/mastitis-part-10-environmental-mastitis/
Strep. uberis is a gram positive bacteria that is very versatile and can be found throughout the environment and survives and grows in bedding, faeces, pasture and the on skin of cows. […] It can cause both clinical and sub clinical cases of mastitis and can cause persistent colonisation of the mammary glands without a subsequent rise in somatic cell counts. […] However, unlike contagious bacteria, preventing cow-to-cow spread during milking will not eliminate environmental mastitis. This is because parlour management does not tackle the route from the environmental source to the cow. […] To control environmental mastitis, a primary focus on environmental hygiene is needed, alongside some parlour management changes. […] E. coli comes from the gut, so anywhere cow faeces can come into contact with the udder, will provide a potential source of coliform mastitis.
#38 Pathogenesis, Diagnosis, Control, and Prevention of Bovine Staphylococcal Mastitis | IntechOpen
https://www.intechopen.com/chapters/79882
Understanding the phenotypic and genotypic requirements for biofilm formation is essential in developing effective treatment against staphylococcal mastitis. […] The dairy cow is exposed to several pathogens daily; the role of innate and adaptive immunity is to remove these pathogens before the infection is established and progresses to disease or further to persistent or chronic infection. […] The pathogenesis of staphylococcal infections depends on several virulence factors that allow them to overcome the hosts immune system. Understanding the detailed pathogenesis of staphylococcal IMI and the hosts innate and adaptive immune responses against IMI is the key to improving mastitis control by vaccine or immunotherapy.
#39
https://gtr.ukri.org/projects?ref=BB%2FE018114%2F1
We will be able to identify a number of proteins from Strep uberis that are essential for disease and these will become components of vaccines to prevent this painful condition. […] After infection with bacteria, animals including humans respond by producing messages in the form of chemicals. […] In the case of mastitis, these chemical messages are responsible such things as attracting specific types of white blood cells from the circulating blood into the mammary gland and for inducing the swelling that leads to pain associated the disease. […] As we now have the possibility of creating infections with avirulent Strep uberis, which do not subsequently result in disease, we can compare the messages produced by the host in response to both virulent and avirulent types of this bacterium.
#40 Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0299234
The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. […] The susceptibility to and development of mastitis is associated with the degree to which mammary glands suffer exposure to pathogenic bacteria. […] Current mastitis treatments include antibiotics, antimicrobial peptides, bacteriophage therapy, probiotics, and nanoparticle-based treatments. […] The broad effectiveness of antibiotics makes them the most popular therapy. However, overreliance on antibiotics contributes to the development of multidrug-resistant bacteria. […] Gong Ying San (GYS) is a classic TCM herbal formulation, composed of Zhe Bei Mu (Fritillariae thunbergii bulbus), Jin Yin Hua (Lonicerae japonicae flos), Lian Qiao (Forsythiae fructus), Tong Cao (Medulla tetrapanacis), Si Gua Lao (loofah) and Pu Gong Ying (dandelion) that has been widely used for mastitis in dairy cows in China.
#41 Therapeutic Effect and Mechanism of Action of Low-molecular-weight Whey Protein Capable of Activating Macrophages in Bovine Mastitis | Anticancer Research
https://ar.iiarjournals.org/content/40/8/4701
Activation of macrophages by LMW-WP has been hypothesized to induce two types of macrophage differentiation. First, it induces differentiation into the M1-type macrophages at the site of infection in the udder tissue and exhibits an antibacterial activity against pathogenic bacteria. Next, since the LMW-WP’s ability to produce VEGF was confirmed, the induction of differentiation into the M2-type macrophages with anti-inflammatory and immunosuppressive functions terminated the tissue damage reaction and repaired the tissue. […] These are two probable reasons why the LMW-WP was able to decrease the number of somatic cells in milk. […] In conclusion, LMW-WP may be an effective therapeutic agent for bovine mastitis because LMW-WP exhibits a growth inhibitory effect on Staphylococcus aureus and Streptococcus, the causative bacteria of bovine mastitis, by inducing the phagocytic activity of macrophages and production of various cytokines.
#42 Changing trends in mastitis | Irish Veterinary Journal | Full Text
https://irishvetjournal.biomedcentral.com/articles/10.1186/2046-0481-62-S4-S59
The global dairy industry, the predominant pathogens causing mastitis, our understanding of mastitis pathogens and the host response to intramammary infection are changing rapidly. […] The genetic basis underlying host adaptation and mechanisms of infection is being unravelled. Genomic information on pathogens and their hosts and improved knowledge of the host’s innate and acquired immune responses to intramammary infections provide opportunities to expand our understanding of bovine mastitis. […] The application of molecular or DNA-based methods in mastitis research and diagnostics has contributed to an increased understanding of mastitis epidemiology and control options. Using these methods, isolates belonging to a bacterial species can be differentiated at the subspecies or strain level, allowing for improved recognition of sources and transmission routes of pathogens.
#43 Changing trends in mastitis | Irish Veterinary Journal | Full Text
https://irishvetjournal.biomedcentral.com/articles/10.1186/2046-0481-62-S4-S59
Through use of genomic and proteomic tools, it will be possible to further explore how different subpopulations of pathogens differ in mechanisms of disease causation and transmission. A more developed understanding of the pathogenesis and epidemiology of bovine mastitis will provide new approaches aimed at improvements in mastitis control. Rapid, effective, and increasingly cost-effective methods of sequencing pathogen genomes have already contributed new information to our understanding of host-pathogen interactions in mastitis. Manipulation of mastitis pathogens using molecular methods such as mutagenesis, and measurement of messenger RNA (transcriptomics), proteins or peptides (proteomics) and networks of metabolites (metabolomics), provide further opportunities to investigate mastitis pathogenesis at pathogen and host level.
#44 Bovine Mastitis: Frontiers in Immunogenetics
https://pmc.ncbi.nlm.nih.gov/articles/PMC4188034/
The important question is how to use this information regarding genetic associations with mastitis and the immune system to actually improve disease resistance. […] It is also worth noting that the immune system, which is the bodys main host defense system, is regulated by thousands of genes. […] In fact, recent information from a human systems biology data base on immunity known as the immunogenetic-related information source IRIS provides evidence for 1,535 immune response genes as of April 2013. […] The ideal solutions to improve resistance to mastitis are likely to be those that focus on a large number of genes, by using information from GWAS, or selection based on breeding values of immune responses, which take into account complex genetic interactions between the innate and adaptive host defense mechanisms without the necessity of knowing all about each individual gene.