Materiały źródłowe

• #1 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9784991/

  Group B Streptococcus (GBS) or Streptococcus agalactiae is a major cause of neonatal mortality. […] Moreover, through continuous evolution, GBS can use its original structure and unique factors to greatly improve its survival rate in the human body. […] This review discusses the key virulence factors that facilitate GBS invasion and colonization and their action mechanisms. […] More than twenty different virulence factors contribute to the GBS pathogenesis. These include adhesins, enzymes, carbohydrates, and other proteins. […] Most of the adhesins mediate GBS colonization in the epithelium of the vaginal tract, enabling its transmission to newborns as they pass through the genital tract at birth. […] Other virulence factors, such as HvgA, hemolytic pigment, and alpha C protein, can facilitate GBS invasion of different tissues, such as the brain, placenta, and cervix, leading to a poorer physical condition.

• #2 Streptococcus Group B – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK553143/

  Group B streptococcus (GBS) commonly appears in up to 35% of healthy women’s reproductive or gastrointestinal tracts. Pregnant women colonized with GBS can transmit the bacteria to their newborns at the time of birth. This infection can lead to neonatal sepsis and/or meningitis. […] The pathogen Streptococcus agalactiae represents group B streptococcus (GBS). The commonly used term of group B streptococcus or GBS is based on Lancefield grouping that takes into account specific cell wall carbohydrate antigens. It is a common colonizer of the genital and gastrointestinal tracts. GBS colonization in pregnant women is a major risk factor for neonatal and infant infection. […] GBS is a gram-positive, catalase-negative organism that appears as cocci in pairs and chains on gram stain. When grown on blood agar, they appear as small colorless colonies that cause beta-hemolysis or complete hemolysis. This is because S agalactiae forms a toxin known as, which causes complete lysis of the hemoglobin in RBCs.

• #3 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://www.mdpi.com/2076-2607/10/12/2483

  Group B Streptococcus (GBS) or Streptococcus agalactiae is a major cause of neonatal mortality. […] This review discusses the key virulence factors that facilitate GBS invasion and colonization and their action mechanisms. […] More than twenty different virulence factors contribute to the GBS pathogenesis. These include adhesins, enzymes, carbohydrates, and other proteins. […] Most of the adhesins mediate GBS colonization in the epithelium of the vaginal tract, enabling its transmission to newborns as they pass through the genital tract at birth. […] Other virulence factors, such as HvgA, hemolytic pigment, and alpha C protein, can facilitate GBS invasion of different tissues, such as the brain, placenta, and cervix, leading to a poorer physical condition. […] This paper will discuss major characterized virulence factors and their involvement in the pathogenesis of GBS.

• #4 Frontiers | Bacterial and Host Determinants of Group B Streptococcal Infection of the Neonate and Infant

  https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.820365/full

  Group B streptococci (GBS) are Gram-positive β-hemolytic bacteria that can cause serious and life-threatening infections in neonates manifesting as sepsis, pneumonia, meningitis, osteomyelitis, and/or septic arthritis. […] The pathogenesis of invasive GBS infections in neonates and infants is complex and there is no single approach to prevent all cases of PTBs, EOD and LOD. […] Understanding mechanisms of GBS invasion and pathogenesis relevant to infections in the neonate and infant may inform the development of therapeutics to prevent or mitigate injury, as well as improve risk stratification. […] GBS encodes a plethora of virulence factors that impact its ability to transition from asymptomatic colonizer to successful invasive pathogen. […] One major factor is the GBS sialylated capsular polysaccharide (CPS), which aids in evasion of host immunity.

• #5 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9784991/

  In gaining access to the blood circulation, GBS can invade the brain epithelium, causing meningitis, one of the late onset diseases (LODs) in newborns, which is fatal. […] A better understanding of these mechanisms has significant implications for overcoming the challenges associated with vaccine development and the development of new treatment regimens for GBS. […] The vagina is thought to be the main reservoir of GBS. […] GBS colonization in the vagina of pregnant women is a major risk to the newborn. […] These virulence factors are associated with dissemination, immune evasion, and damage to tissue, and allow GBS survival in the hostile vaginal environment. […] The first step for GBS colonization of the vagina is the adhesion to its epithelial cells via surface-associated adhesins.

• #6 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://www.mdpi.com/2076-2607/10/12/2483

  A better understanding of these mechanisms has significant implications for overcoming the challenges associated with vaccine development and the development of new treatment regimens for GBS. […] The vagina is thought to be the main reservoir of GBS. […] GBS colonization in the vagina of pregnant women is a major risk to the newborn. […] The first step for GBS colonization of the vagina is the adhesion to its epithelial cells via surface-associated adhesins. […] Several adhesion factors enable GBS to bind to components of the extracellular matrix (ECM), thereby enhancing its ability to penetrate the host mucosal barrier and spread to other host tissues. […] GBS strains also possess the conserved “housekeeping” sorting enzyme A (SrtA), which is involved in the covalent assembly of pili on the cell wall.

• #7 Virulence Factors of Group B Streptococcus | Encyclopedia MDPI

  https://encyclopedia.pub/entry/39856

  Group B Streptococcus (GBS) or Streptococcus agalactiae is a major cause of neonatal mortality. When colonizing the lower genital tract of pregnant women, GBS may cause premature birth and stillbirth. If transmitted to the newborn, it may result in life-threatening illnesses, including sepsis, meningitis, and pneumonia. Moreover, through continuous evolution, GBS can use its original structure and unique factors to greatly improve its survival rate in the human body. […] The vagina is thought to be the main reservoir of GBS. GBS colonization in the vagina of pregnant women is a major risk to the newborn. These virulence factors are associated with dissemination, immune evasion, and damage to tissue, and allow GBS survival in the hostile vaginal environment. […] The first step for GBS colonization of the vagina is the adhesion to its epithelial cells via surface-associated adhesins. Several adhesion factors enable GBS to bind to components of the extracellular matrix (ECM), thereby enhancing its ability to penetrate the host mucosal barrier and spread to other host tissues.

• #8 Streptococcus agalactiae – Wikipedia

  https://en.wikipedia.org/wiki/Streptococcus_agalactiae

  GBS is the leading cause of bacterial neonatal infection in the baby during gestation and after delivery with significant mortality rates in premature infants. […] GBS infections in the mother can cause chorioamnionitis (a severe infection of the placental tissues) infrequently, postpartum infections (after birth) and it had been related with prematurity and fetal death. […] GBS neonatal infection typically originates in the lower reproductive tract of infected mothers. […] GBS infections in newborns are separated into two clinical syndromes, early-onset disease (EOD) and late-onset disease (LOD). […] EOD is acquired vertically (vertical transmission), through exposure of the fetus or the baby to GBS from the vagina of a colonized woman, either intrautero or during birth after rupture of membranes.

• #9 Streptococcus agalactiae – Wikipedia

  https://en.wikipedia.org/wiki/Streptococcus_agalactiae

  GBS LOD affects infants from 7 days to 3 months of age and is more likely to cause bacteremia or meningitis. […] GBS is also an important infectious agent able to cause invasive infections in adults. […] Serious life-threatening invasive GBS infections are increasingly recognized in the elderly and individuals compromised by underlying diseases such as diabetes, cirrhosis and cancer.

• #10 Prevention of Group B Streptococcal Early-Onset Disease in Newborns | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns

  Group B streptococcus (GBS) is the leading cause of newborn infection. The primary risk factor for neonatal GBS early-onset disease (EOD) is maternal colonization of the genitourinary and gastrointestinal tracts. Approximately 50% of women who are colonized with GBS will transmit the bacteria to their newborns. Vertical transmission usually occurs during labor or after rupture of membranes. In the absence of intrapartum antibiotic prophylaxis, 12% of those newborns will develop GBS EOD. Other risk factors include gestational age of less than 37 weeks, very low birth weight, prolonged rupture of membranes, intraamniotic infection, young maternal age, and maternal black race. […] The key obstetric measures necessary for effective prevention of GBS EOD continue to include universal prenatal screening by vaginalrectal culture, correct specimen collection and processing, appropriate implementation of intrapartum antibiotic prophylaxis, and coordination with pediatric care providers.

• #11 Streptococcus Group B – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK553143/

  In pregnant women colonized with S agalactiae, bacteria can ascend from the genitourinary tract towards the uterus or bladder. In the uterus, the bacteria can affect the fetal membranes, causing chorioamnionitis, potentially leading to premature labor, miscarriage, or intrauterine fetal demise if the bacterium invades the neonate. Alternatively, the bacterium may invade the newborn’s respiratory tract by way of amniotic fluid or contact with the maternal colonization during vaginal delivery, causing inflammation of the lung tissue or GBS pneumonia. […] GBS remains the primary cause of neonatal sepsis since the 1970s. […] The initial therapy for suspected neonatal sepsis is ampicillin and an aminoglycoside, typically gentamicin. Both ampicillin and gentamicin have activity against GBS, which is the most common cause of neonatal sepsis.

• #12 Specific Bacterial Infections: Group B Streptococcus | GLOWM

  https://www.glowm.com/section-view/heading/Specific%20Bacterial%20Infections:%20Group%20B%20Streptococcus/item/179

  The low attack rate of serious neonatal GBS infection, despite a high prevalence of maternal and neonatal GBS colonization, suggests considerable protection against invasive infection. GBS has been associated with both AF infection and neonatal sepsis diagnosed at birth, indicating that infection occurs before birth. In fact, approximately 70% of infants with early-onset GBS infection are bacteremic at birth. This indicates that bacteremia develops in utero as a result of aspiration of infected AF, or contamination of umbilical blood due to a GBS-infected placenta. The chorioamnion provides an anatomic barrier against infection. AF also contains several factors that are antibacterial, including peroxidase, lysozyme, transferrin, immunoglobulins, complement, and a zinc-dependent bactericidal polypeptide. The attack rate of GBS infection, however, is increased in the setting of preterm labor, and GBS can be isolated from the AF of patients in preterm labor with intact membranes, suggesting that GBS can cross the intact chorioamnion. Rupture of membranes (ROM) allows vaginal bacteria to enter into AF, and as expected, the attack rate of GBS infection increases with prolonged ROM. The risk of clinical AF infection is increased in the presence of the following: GBS colonization, ROM lasting more than 6 hours, internal fetal monitoring lasting more than 12 hours, and more than six vaginal examinations.

• #13 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9784991/

  GBS capsules consist mainly of carbohydrates with the capsule polysaccharide synthesis (CPS) operon driving its synthesis. […] Streptococcal polysaccharide capsules defend bacterial cells from deposition of complement, opsonization, and phagocytosis. […] Capsules contain the 2,3-linked sialic acid (Sia) residues, which are analogs to a human cell surface glycocomplex epitope. […] The alpha C protein (ACP) is the prototype of a family of Gram-positive bacterial surface proteins. […] It facilitates the entry of GBS into human cervical epithelial cells and traverses the cell layer by binding to glycosaminoglycans (GAG) on the surface of the host cell. […] GBS evolved a set of virulence factors, including adhesins and hemolytic pigments, to promote its ability to colonize and invade human hosts.

• #14 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://www.mdpi.com/2076-2607/10/12/2483

  In addition to the capsule, the pilus has now been identified as an essential factor in increasing the pathogenicity of GBS. […] The alpha C protein (ACP) is the prototype of a family of Gram-positive bacterial surface proteins. […] GBS capsules consist mainly of carbohydrates with the capsule polysaccharide synthesis (CPS) operon driving its synthesis. […] Streptococcal polysaccharide capsules defend bacterial cells from deposition of complement, opsonization, and phagocytosis. […] GBS evolved a set of virulence factors, including adhesins and hemolytic pigments, to promote its ability to colonize and invade human hosts. […] While there has been a great deal of research in recent years to improve our understanding of GBS, more exploration is still needed on the structure of some of the pathogenic factors of GBS and how it survives as both a symbiont and a pathogen.

• #15 Cell Surface and Cytosolic Proteins of Group B Streptococcus Adding New Dimensions in Its Colonization and Pathogenesis | IntechOpen

  https://www.intechopen.com/chapters/70554

  The colonization and breaching of mucosal surfaces by GBS thus allows its entry to normally sterile sites like blood stream, CNS and fetal membranes. […] The main virulence factor of GBS is thought to be pore forming toxins (Beta hemolysins/cytolysins and CAMP factor) and sialic acid rich CPS. […] Their virulence potential is because of its antiphagocytic properties. […] The CPS also has a pivotal role in preventing complement activation, therefore does not influence adherence of GBS to epithelial cells but does reduce internalization. […] Despite the advancement of the understanding about various virulence factors, their understanding on the regulation and use of these virulence tools has not yet been much explored. […] The exclusive clinical features of GBS infection pose several questions that provide an agenda for hypothesis development (a hypothetical model) and experimental testing.

• #16 Streptococcus agalactiae – Wikipedia

  https://en.wikipedia.org/wiki/Streptococcus_agalactiae

  Streptococcus agalactiae is a gram-positive coccus (round bacterium) with a tendency to form chains (as reflected by the genus name Streptococcus). […] GBS are surrounded by a bacterial capsule composed of polysaccharides (exopolysaccharide). […] GBS harbors an important number of virulence factors (virulence factors are molecules produced by bacteria that boosts their capacity to infect and damage human tissues), the most important being the capsular polysaccharide (rich in sialic acid) and a pore-forming toxin, -hemolysin. […] By expressing an unusually high amount of sialic acid on the bacterial cell surface, S. agalactiae can subvert the innate immune system, convincing leukocytes that the bacteria are human cells. […] GBS colonization of the vagina usually does not cause problems in healthy women, nevertheless during pregnancy it can sometimes cause serious illness for the mother and the newborn.

• #17 Streptococcus agalactiae | Mechanisms of Pathogenicity

  https://mechpath.com/2021/11/16/streptococcus-agalactiae/

  Immune evasion factors such as sialic acid capsular polysaccharide or superoxide dismutase are proteins that make the bacteria resist the immune system. […] S. agalactiae can resist AMPs by the alanylation of lipoteichoic acid, which is a negatively charged molecule on the bacteria surface that is the target of AMPs. […] Cell-adhesion and invasion factors like fibrinogen-binding proteins A and B simply aid in the adhesion of the bacteria to the host cell and in the penetration process.

• #18 Streptococcus Group B – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK553143/

  GBS has several virulence factors that help it attach to the host cells and evade the immune system. This bacterium is encapsulated by a polysaccharide layer rich in sialic acid, which is a substance also found in human cells. Thus, inexperienced immune cells in a newborn may confuse S agalactiae for self-cells, allowing them to survive inside the body. A type-specific capsular polysaccharide is released from cells, and the amount elaborated has been correlated with virulence. […] GBS can be found colonizing normal gastro-intestinal and genitourinary flora in up to one-third of healthy asymptomatic women. Several factors associated with a higher risk of colonization include Black race, obesity, multiple sexual partners, man-to-woman oral sex, frequent sexual intercourse, tampon use, and infrequent hand washing.

• #19 Frontiers | Bacterial and Host Determinants of Group B Streptococcal Infection of the Neonate and Infant

  https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.820365/full

  Serotype III is a major contributor to the burden of neonatal disease accounting for 62% of fetal and neonatal disease cases. […] This tight correlation between ST-17 and invasive neonatal disease stems from the presence of multiple mobile genetic elements that harbor ST-17-specific virulence factors, including the GBS surface adhesin HvgA that facilitates invasion of the neonatal brain. […] The pathogenesis of GBS invasive disease is reliant on the organism’s ability to overcome host barriers. […] GBS expresses a variety of virulence factors including CPS, hemolytic pigment, adhesins and extracellular enzymes that can act in concert to subvert, counteract, or promote immune responses conducive to GBS dissemination in the neonate.

• #20 Group B Streptococcal Meningitis: A Description of Six Case Reports | Coni | International Journal of Clinical Pediatrics

  https://www.theijcp.org/index.php/ijcp/article/view/179/152

  Group B Streptococcus (GBS) is classified into eight serotypes (Ia, II, III, IV, V, VI, VII, and VIII) on the basis of capsular polysaccharide and presence/absence of c and R protein antigens. The EOD can be caused by all serotypes while serotype III is the one most responsible for LOD (90% of cases) […] Furthermore, serotype III is the one mainly responsible for cases of GBS meningitis, regardless of the age at onset of infection. The development of GBS meningitis reflects the ability of the bacteria to invade the microvascular endothelial cells of the human brain (brain microvascular endothelial cells (BMECs)). The first step in the pathogenesis of meningitis consists of the interaction between GBS and BMECs. GBS can gain access through the CNS by direct lysis of BMECs with consequent endothelial damage, inflammation and disruption of the integrity of the BBB or, alternatively, by bacterial transcytosis. Several virulence factors are thought to be involved in the pathogenesis of meningitis: SRR1 and SRR2 (serine-rich repeat glycoprotein) […] the HvgA (hypervirulent GBS adhesin) […] the Lmb (laminin-binding protein), and LagA (lipoteichoic acid anchoring enzyme). Reactive nitrogen species are the most important mediators of brain inflammation. Eventually, GBSs can reach the brain through choroid plexus or intraventricular hemorrhage.

• #21 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9784991/

  Several adhesion factors enable GBS to bind to components of the extracellular matrix (ECM), thereby enhancing its ability to penetrate the host mucosal barrier and spread to other host tissues. […] Srr1/Srr2 are structurally characterized by an extended N-terminal signal sequence, two highly glycosylated serine-rich repeats (Srr), at least one non-repeat binding region (BR), and a C-terminal cell wall anchoring domain carrying the LPxTG (Leu-Pro-x-Thr-Gly) pattern. […] The GBS Srr family of glycoproteins as surface-associated fibrinogen binding proteins (Fbs) binds to a single tandem repeat region of human fibrinogen via a lock, dock and latch mechanism. […] This binding leads to a series of ordered conformational changes in Srr and results in enhanced adhesion to the target cells. […] Clonal complex (CC)-17 strains (capsular serotype III) are highly virulent producers of the Srr2.

• #22 Group B Streptococcus: Virulence Factors and Pathogenic Mechanism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9784991/

  Most GBS clinical strains express Srr1, which binds to fibrinogen and keratin 4 and thereby mediates adhesion to the vaginal and cervical epithelium. […] Srr1 glycosylation enhances the stability of Srr1 by resisting protease inactivation, thereby prolonging adhesion and persistence. […] The plasminogen binding surface protein (PbsP) is a surface protein with crucial functions in GBS pathophysiology. […] This adhesion protein has two streptococcal surface repeat structural domains, a methionine- and lysine-rich region, and an LPxTG cell wall anchoring pattern, mediating plasminogen binding to enhance the ability to colonize and invade host tissues. […] The finding of the MK-rich domain and Kringle 4 LBS may provide a new direction for vaccine development. […] In addition to the capsule, the pilus has now been identified as an essential factor in increasing the pathogenicity of GBS.

• #23 Cell Surface and Cytosolic Proteins of Group B Streptococcus Adding New Dimensions in Its Colonization and Pathogenesis | IntechOpen

  https://www.intechopen.com/chapters/70554

  With a big pool of virulence factors encrypted by GBS, it has been confirmed to adhere to a variety of eukaryotic cellular structures. […] The initial step of adherence is thought to be mediated by a number of bacterial moieties such as laminin binding proteins, C5a peptidase, glyceraldehyde phosphate dehydrogenase, -enolase and lipoteichoic acid. […] Recently, GBS were revealed to express filamentous cell surface appendages known as pili. […] Pili mediate GBS resistance to AMPs (antimicrobial peptides) and also aid in its attachment to the host cells. […] Upon bacterial binding to the host cell receptors, recruitment of host-cell actin to the site of bacterial entry has been observed. […] However, there are some studies which have shown that certain bacterial surface proteins like type III CPS and the N-terminal region of the alpha C protein partially mask the specific components of GBS that are critical for adherence/invasion of eukaryotic cells.

• #24 Virulence Factors of Group B Streptococcus | Encyclopedia MDPI

  https://encyclopedia.pub/entry/39856

  The plasminogen binding surface protein (PbsP) is a surface protein with crucial functions in GBS pathophysiology. This adhesion protein has two streptococcal surface repeat structural domains, a methionine- and lysine-rich region, and an LPxTG cell wall anchoring pattern, mediating plasminogen binding to enhance the ability to colonize and invade host tissues. […] HylB can cleave the high-molecular-weight glycosaminoglycan polymer of hyaluronic acid, which serves as the epithelial extracellular matrix component. HylB cleavage of hyaluronic acid breaks the maternal–fetal barrier and enables the travel of GBS from the vagina to the fetus to cause fatal infection and damage. […] Hemolytic activity in GBS is due to the ornithine rhamnolipid pigment (hereafter called “hemolytic pigment” or “pigment”, also known as Granadaene), which is produced by the genes of the cyl operon.

• #25 Mechanisms of group B Streptococcus-mediated preterm birth: lessons learnt from animal models in: Reproduction and Fertility Volume 3 Issue 3 (2022)

  https://raf.bioscientifica.com/view/journals/raf/3/3/RAF-21-0105.xml

  An important step in GBS pathogenesis is its anterograde transition from the vagina to the fetal sac. […] In this study, competition assays demonstrated a marked advantage to H/C-expressing GBS during colonization. […] The results indicated that GBS infection-mediated fetal death is associated with the production of hemolytic pigment and the presence of NLRP3 inflammasome. […] The ascended bacteria need to break the maternal-fetal barrier so as to reach the fetus to cause serious infection and damage. […] This immune suppression mediated by HylB can help GBS to escape from immune responses, and this could result in devastating effects like preterm births and fetal injury. […] Recent studies on C57BL/6 and CD-1 revealed that in type II GBS, endonuclease effector Cas9, which is a part of CRISPR/Cas locus, plays an important role in vaginal persistence and disease.

• #26 Streptococcus agalactiae (GBS): Properties, Pathogenesis, Lab Diagnosis • Microbe Online

  https://microbeonline.com/streptococcus-agalactiae-gbs-properties-pathogenesis-diagnosis/

  Polysaccharide capsular antigens: Inhibits activation of the alternative complement cascade and prevents phagocytosis […] C5a peptidase produced by the streptococci cleave complement component C5a and interfere with C5a-mediated neutrophil chemotaxis. This peptidase also binds to fibronectin and serves as a bacterial adhesin and invasin […] Beta-hemolysin/cytolysin: Pore-forming hemolysin that is able to lyse pulmonary alveolar epithelial and endothelial cells and plays a role in neonatal lung infection and subsequent sepsis. […] Lipoteichoic acid: Participate in facilitating adherence as the first step in infection. […] Cell surface proteins: C antigen: May mediate internalization of organisms within human cervical epithelial cells following attachment. […] Protect organisms from intracellular killing following phagocytosis

• #27 Streptococcus agalactiae (GBS): Properties, Pathogenesis, Lab Diagnosis • Microbe Online

  https://microbeonline.com/streptococcus-agalactiae-gbs-properties-pathogenesis-diagnosis/

  Cell surface penicillin-binding protein (PBP 1a): Enables streptococcal cells to resist intracellular killing by phagocytic cells. […] Hyaluronic acid lyase: This may act to spread infection by the breakdown of hyaluronic acid in the extracellular matrix, and may act on the hyaluronic acid present in concentrations in placental tissues, fetal tissues, and amniotic fluids. […] Rectovaginal colonization of Streptococcus agalactiae is found in 10% to 37% of pregnant women which may be transient, intermittent, or persistent. The presence of group B streptococci in the female genital tract at the time of birth can lead to infection of the neonate. Streptococcus agalactiae is a predominant cause of acute meningitis in neonates. […] Neonatal disease with group B streptococci follows two patterns, termed early-onset disease and late-onset disease.

• #28 Cell Surface and Cytosolic Proteins of Group B Streptococcus Adding New Dimensions in Its Colonization and Pathogenesis | IntechOpen

  https://www.intechopen.com/chapters/70554

  Some advancement in knowledge of pathogenesis has been achieved through development of cell culture systems and animal models. […] However, not much about the cytosolic proteins of GBS is known. […] The process of human infection by group B Streptococcus (GBS) is complex and multifactorial. […] Their entry and survival inside the respiratory epithelial cells may represent a mechanism by which these bacteria gain access into the blood circulation. […] Streptococcal surface-associated proteins are critically important in the host- pathogen relationship as they can provide initial contact of the bacteria with its intended host before internalization. […] A cell surface protease CspA, targets host fibrinogen producing adherent fibrin like cleavage products that coat the bacterial surface and interfere with opsonophagocytic clearance.

• #29 Mechanisms of Group B Streptococcus Colonization and Ascending Infection

  https://digital.lib.washington.edu/researchworks/items/5dcf4a93-d514-4eac-b4ba-e036d4c53813

  GBS virulence is largely mediated by its unique hemolytic toxin which is a pigmented rhamnolipid (hereafter-called hemolytic pigment); yet hyper-pigmented GBS strains are rarely isolated from vagina. […] Once GBS has ascended from the vagina to infect the placenta, the hemolytic pigment is required for resistance of the host immune response, and hyper-pigmented strains are more resistant to killing by host immune defenses. […] These data indicate that a delicate balance of hemolytic pigment expression, and therefore regulation of the host immune response, is necessary for successful colonization and ascending infection. […] We show that GBS interactions with vaginal epithelial cells play an integral role in permitting ascending infection. […] GBS stimulate a process known as epithelial exfoliation that is critical for ascending infection.

• #30 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20180411/Study-uncovers-mechanism-fueling-group-B-strep-infection-in-womans-uterus.aspx

  Group B strep (group B streptococcus or GBS) is a common bacteria present in the vagina of about 1 in 4 women. […] Despite the substantial impact on pregnancy outcomes, scientists know little about how GBS establishes an in utero infection. […] Rajagopal’s lab found that GBS takes advantage of exfoliation, a response to infection previously thought to protect against invasive infection. Rather than preventing infection by shedding infected cells from tissue, GBS-induced exfoliation activates a signaling pathway that allows the bacteria to permeate the vaginal barrier and infect the uterus.

• #31

  https://www.jci.org/articles/view/97043

  Group B streptococcus (GBS) is part of the normal vaginal flora of approximately 25% of healthy women. […] GBS promotes shedding of the vaginal epithelium, which in turn increases bacterial dissemination and ascending GBS infection. […] GBS induces vaginal epithelial exfoliation by activation of integrin and -catenin signaling. […] GBS-induced epithelial exfoliation had no impact on vaginal colonization, but rather permitted bacterial dissemination and ascending infection. […] Our study shows that preventing GBS-induced exfoliation by blocking upstream integrin signaling decreases ascending infection and improves pregnancy outcomes. […] GBS stimulates vaginal epithelial exfoliation by activating integrin and -catenin signaling, leading to the loss of barrier function and epithelial-to-mesenchymal transition (EMT) in vaginal epithelial cells.

• #32

  https://www.jci.org/articles/view/97043

  GBS infection of hVECs induced the phosphorylation of GSK3, which prevents cytoplasmic degradation of -catenin, leading to its nuclear translocation. […] GBS are able to stimulate integrin signaling, which permits nuclear translocation of -catenin, potentially leading to EMT, barrier disruption, and vaginal epithelial exfoliation. […] GBS induction of epithelial exfoliation and loss of barrier function are a result of integrin activation and induction of -catenin signaling and EMT.

• #33 A new mechanism used by group B Streptococcus to evade the host immune system | Institut Pasteur

  https://www.pasteur.fr/en/research-journal/news/new-mechanism-used-group-b-streptococcus-evade-host-immune-system

  Streptococcus agalactiae. Institut Pasteur News 2016.07.13 Print | Share LinkedIn logo Facebook logo Research […] Pathogenic bacteria produce a number of molecules that can be recognized by the innate immune system. […] Scientists from the Institut Pasteur and the CNRS, in cooperation with the University of Massachusetts Medical School, have demonstrated that group B Streptococcus degrades one of these molecules so that it can control the inflammatory response of the infected host. […] Scientists from the Biology of Gram-Positive Pathogens Unit, directed by Patrick Trieu-Cuot (Institut Pasteur/CNRS), working together with scientists from the University of Massachusetts, discovered a new mechanism that enables bacteria to limit interferon production by infected immune cells. The production of interferon following GBS infection mainly depends on the cells recognizing two types of molecule released by the bacteria: bacterial DNA and cyclic di-AMP, a specific signaling nucleotide which controls the activity of many of the bacteria’s vital functions. […] CDNP thereby controls interferon production and boosts the pathogen’s virulence. […] This original mechanism, in which bacteria degrade their own molecules to avoid being recognized by the immune system, may also exist in other pathogens.

• #34 Mechanisms of Group B Streptococcus Colonization and Ascending Infection

  https://digital.lib.washington.edu/researchworks/items/5dcf4a93-d514-4eac-b4ba-e036d4c53813

  To induce epithelial exfoliation, GBS actives a class of proteins called integrins, which leads to -catenin signaling and epithelial-to-mesenchymal transition (EMT), resulting in a migratory cell phenotype. […] Reduction of integrin activation results in less epithelial exfoliation and a reduction in ascending infection and adverse pregnancy outcomes. […] Finally, we endeavored to define the mechanism by which GBS establishes in utero infection. […] The GBS hyaluronidase, HylB, is a secreted enzyme that cleaves the host extra-cellular matrix molecule hyaluronic acid into is disaccharide moiety. […] Hyaluronic acid disaccharides have the ability to block toll-like receptors, which are critical for the detection of pathogenic bacteria, and thus prevent immune recognition of GBS. […] Using a murine model of ascending infection, we show that GBS deficient for hylB have reduced ability to establish in utero infections due to increased immune recognition of the bacteria. […] Together, the work in this dissertation describes how GBS successfully colonizes the vagina, ascends from the vagina into the pregnant uterus, and blunts the host immune response in the uterus, leading to placental and fetal infection and adverse pregnancy outcomes.

• #35 Group B streptococcal membrane vesicles induce proinflammatory cytokine production and are sensed in an NLRP3 inflammasome-dependent mechanism in human macrophages | bioRxiv

  https://www.biorxiv.org/content/10.1101/2022.08.10.503555v1.full

  Group B Streptococcus (GBS) is a major cause of fetal and neonatal mortality worldwide. Many of the adverse effects associated with invasive GBS are associated with inflammation that leads to chorioamnionitis, preterm birth, sepsis, and meningitis; therefore, understanding bacterial factors that promote inflammation is of critical importance. […] Here, we hypothesized that macrophages respond to GBS-derived MVs by producing proinflammatory cytokines and are recognized through one or more pattern recognition receptors. […] These data indicate that MVs contain one or more pathogen-associated molecular patterns that can be sensed by the immune system. Furthermore, this study identifies the NLRP3 inflammasome as a novel sensor of GBS MVs. […] We also identified NLRP3 as a sensor of GBS derived MVs.

• #36 Mechanisms of group B Streptococcus-mediated preterm birth: lessons learnt from animal models in: Reproduction and Fertility Volume 3 Issue 3 (2022)

  https://raf.bioscientifica.com/view/journals/raf/3/3/RAF-21-0105.xml

  Understanding the mechanisms of infection by GBS will be crucial in developing drugs and vaccines to protect against the harmful effects of the bacteria. […] The ability of GBS to persist in the mouse vaginal tract varies among the serotypes infected. The GBS strain, CJB111 (serotype V), persisted beyond several weeks in 50% of mice while GBS strains A909 (serotype Ia) and COH1 (serotype III) persisted for about 12 weeks. […] Thus, the cause of such differential ability to colonize needs to be identified. […] The GBS MVs can internalize in a range of cell lines including HeLa, human lung epithelial cell line (A549), human keratinocyte cell line (HaCaT), differentiated macrophage-like cells (dTHP-1), and murine dendritic DC2.4. […] The GBS MVs are enriched with nucleic acids, certain lipids, and virulent factors including hyaluronate lyases, C5a peptidase, and sialidases.

• #37 The CovR regulatory network drives the evolution of Group B Streptococcus virulence | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009761

  The major regulator of host-pathogen interaction in -hemolytic streptococci is the transcriptional factor CovR belonging to the OmpR family of bacterial response regulator. […] Targeted analysis in GBS demonstrated that CovR directly represses the transcription of the cyl operon encoding the -h/c toxin, the bibA gene, and the PI-1 pili operon. […] The activity of CovR is modulated by its cognate histidine kinase CovS, which has a dual kinase and phosphatase activity on a conserved D53 aspartate residue. […] In addition, a genomic analysis has highlighted mutational biases in the CovR/S system itself and in the CovR regulated promoters in CC-17 strains, suggestive of a positive selection acting on the CovR regulatory pathway in hypervirulent clones. […] To address the role of CovR in GBS hypervirulent clones, we characterized the CovR regulon in a CC-17 strain and demonstrated the direct regulation of a combination of proteins involved in host-pathogen interaction.

• #38 The CovR regulatory network drives the evolution of Group B Streptococcus virulence | PLOS Genetics

  https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009761

  The plasticity of the CovR regulatory network generates phenotypic heterogeneity at the species level, thus allowing the selection of clones associated to specific hosts and pathological conditions. […] At the functional level, CovR directly represses cell-wall and secreted proteins involved in GBS pathogenesis, including the HvgA, FbsA, PbsP, and Pil-1 adhesins, the C5a peptidase ScpB and related serine proteases, and the secreted NucA endonuclease and FbsB adhesin. […] The direct regulon might also include the gene encoding the FbsC adhesin. […] However, since the FbsC adhesin is not functional due to conserved frameshift mutations in CC-17 strains, we did not investigate further its co-regulation with the BQ8897_RS04625 gene. […] Our strict definition of the CovR direct regulon encompassed 21 out of the 62 chromosomal binding sites. The remaining binding sites were sorted into a larger regulon consisting of 3 groups.

• #39 Transcriptome Adaptation of Group B Streptococcus to Growth in Human Amniotic Fluid | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006114

  Streptococcus agalactiae (group B Streptococcus) is a bacterial pathogen that causes severe intrauterine infections leading to fetal morbidity and mortality. The pathogenesis of GBS infection in this environment is poorly understood, in part because we lack a detailed understanding of the adaptation of this pathogen to growth in amniotic fluid. […] We have discovered that GBS significantly remodels its transcriptome in response to exposure to human amniotic fluid. […] The majority of the observed changes in transcripts affects genes involved in basic bacterial metabolism and is connected to AF composition and nutritional requirements of the bacterium. Importantly, the response to growth in human AF included significant changes in transcripts of multiple virulence genes such as adhesins, capsule, and hemolysin and IL-8 proteinase what might have consequences for the outcome of host-pathogen interactions.

• #40 Transcriptome Adaptation of Group B Streptococcus to Growth in Human Amniotic Fluid | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006114

  Our work provides extensive new information about how the transcriptome of GBS responds to growth in AF, and thus new leads for pathogenesis research. […] Compared to other pathogenic streptococci such as GAS, virulence factors of GBS are much less studied and therefore not well understood. However, we observed differential expression of multiple putative cell wall anchored proteins and proven virulence factors. […] The observation that many genes encoding adhesions are down-regulated, and genes encoding known virulence factors such as a hemolysin and a potent IL-8 proteinase are up-regulated likely have consequences for the outcome of host-pathogen interactions.

• #41 Specific Bacterial Infections: Group B Streptococcus | GLOWM

  https://www.glowm.com/section-view/heading/Specific%20Bacterial%20Infections:%20Group%20B%20Streptococcus/item/179

  A potentially effective deterrent to invasive infection may be maternal antibodies directed against the capsular polysaccharide antigens of GBS. Immunity to GBS is mediated by antibody-dependent phagocytosis. Mothers of infants with type III GBS sepsis have lower serum levels of type-specific antibodies than women giving birth to asymptomatically colonized infants. The type III IgG antibody has some broad reactivity to all GBS, and it readily crosses the placenta. When measured in mother-infant pairs, an excellent correlation exists between maternal and cord antibody levels. More than 73% of GBS-colonized mothers with healthy neonates were found to have high type III serum antibody in contrast to only 19% of GBS-colonized mothers whose neonates acquired early-onset septicemia or meningitis. However, GBS acts as a poor immunogen. GBS colonization and even invasive GBS infection in the neonate often fails to produce serum antibody against GBS in the mother or the neonate. This explains why neonatal GBS infection can occur in subsequent pregnancies.

• #42

  https://link.springer.com/article/10.1007/s15010-024-02210-3

  Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. […] The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. […] The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. […] Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease. […] The increase in the incidence of invasive GBS infection found in this study is similar to what has been reported elsewhere. […] An aging population with increasing prevalence of comorbid diseases has been pointed out as the main reason for the increasing burden of invasive GBS disease.

• #43

  https://link.springer.com/article/10.1007/s15010-024-02210-3

  We found a significant rise in proportion of GBS patients with type 2 diabetes, cancer, cardiovascular and neurological diseases. […] The pathophysiological mechanisms by which diabetes leads to higher susceptibility to invasive GBS is proposed to be modulation of the immune system and weakening of anatomic barriers. […] The differentiation between type 1 and type 2 diabetes in relation to invasive GBS disease has to our knowledge not been reported before. […] The change in relative distribution of CPS types during the study period corresponds with changes over time reported from the US and Canada.

• #44 About Group B Strep Disease | Group B Strep | CDC

  https://www.cdc.gov/group-b-strep/about/index.html

  GBS bacteria can cause many types of infections. Some of these infections can be life threatening. […] GBS bacteria most commonly cause bacteremia, sepsis, pneumonia, and meningitis in newborns. […] Bloodstream infections, pneumonia, and skin and bone infections are the most common GBS infections among men and non-pregnant women. It’s very uncommon for GBS bacteria to cause meningitis in adults. […] GBS bacteria come and go naturally in peoples bodies. How people spread GBS bacteria to others is generally unknown. […] Pregnant women can pass the bacteria to their babies during delivery. Most babies who get GBS disease in the first week of life are exposed to the bacteria this way. […] There are currently no vaccines to prevent GBS disease, but they are under development. […] Healthcare providers usually treat GBS disease with antibiotics. Sometimes people with soft tissue and bone infections may need additional treatment, such as surgery. Treatment will depend on the type of infection caused by the GBS bacteria.

• #45 Group B strep infection | March of Dimes

  https://www.marchofdimes.org/find-support/topics/planning-baby/group-b-strep-infection

  Group B streptococcus (also called Group B strep or GBS) is a common type of bacteria (tiny organisms that live in and around your body) that can cause infection. […] If you have GBS during childbirth and its not treated, there is a 1 to 2 percent chance that your baby will get the infection. […] If you have GBS and youre given antibiotics during labor and birth, your treatment helps protect your baby from the infection. […] Treatment with antibiotics helps prevent your baby from getting the infection. […] If you have GBS, you can pass this kind of infection to your baby during or after birth. […] Treatment with antibiotics during labor and birth does not prevent late-onset GBS. […] Babies with a GBS infection can have one or more of these illnesses: Sepsis, a blood infection; Pneumonia, a lung infection; Meningitis, an infection of the fluid and lining around the brain.

• #46 Streptococcus agalactiae (GBS): Properties, Pathogenesis, Lab Diagnosis • Microbe Online

  https://microbeonline.com/streptococcus-agalactiae-gbs-properties-pathogenesis-diagnosis/

  Early-onset disease: is associated with in utero or perinatal (during passage through a birth canal that is colonized with group B streptococci) organism acquisition. […] Late-onset-disease: acquired from the birth canal of colonized mothers or from postnatal acquisition from the mother, other caregivers, or nosocomially.

• #47 Group B strep infection | March of Dimes

  https://www.marchofdimes.org/find-support/topics/planning-baby/group-b-strep-infection

  But babies infected with early-onset GBS or late-onset GBS are treated with antibiotics through an IV, and are kept in the hospital until the cultures are negative. […] GBS can cause a uterine infection during and after pregnancy. […] If you have a UTI caused by GBS, your provider gives you antibiotics to take by mouth during pregnancy.

• #48 Streptococcus Group B – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK553143/

  Intrapartum antibiotic prophylaxis (IAP) is indicated for all mothers with a positive GBS screening culture routinely obtained at 35 to 37 weeks gestation. Revised guidelines from 2010 also recommend IAP for pregnant women who have a history of GBS bacteriuria at any point during the current pregnancy or have a history of a previous infant with invasive GBS disease.

• #49 Prevention of Group B Streptococcal Early-Onset Disease in Newborns | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns

  Targeted intravenous intrapartum antibiotic prophylaxis has demonstrated efficacy for prevention of GBS early-onset disease (EOD) in neonates born to women with positive antepartum GBS cultures and women who have other risk factors for intrapartum GBS colonization. Neither antepartum nor intrapartum oral or intramuscular regimens have been shown to be comparably effective in reducing GBS EOD. […] Vaginalrectal colonization with GBS at the time of labor onset is the most important risk factor for neonatal GBS EOD, and a universal culture-based screening strategy for identifying candidates for GBS intrapartum antibiotic prophylaxis was demonstrated to be superior to risk-based screening protocols for the prevention of GBS EOD. […] Group B streptococcus can transition from an asymptomatic commensal member of the mucosal biome to a pathogenic bacterium under certain conditions. The organism may cause maternal urinary tract infection, intraamniotic infection, or endometritis and is associated with preterm labor and stillbirth.

• #50 Prevention of Group B Streptococcal Early-Onset Disease in Newborns | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns

  The present guidelines are designed to lower the risk of GBS EOD, which is the most common cause of early-onset neonatal sepsis. […] Approximately 50% of women who are colonized with GBS will transmit the bacteria to their newborns. In the absence of intrapartum antibiotic prophylaxis, 12% of those newborns will develop GBS EOD. […] The primary risk factor for neonatal GBS EOD is maternal vaginalrectal colonization with GBS during the intrapartum period. Other risk factors include gestational age less than 37 weeks, very low birth weight, prolonged rupture of membranes, intraamniotic infection, young maternal age, and maternal black race. […] Targeted intravenous intrapartum antibiotic prophylaxis has demonstrated efficacy for prevention of GBS EOD in neonates born to women with positive antepartum GBS cultures and women who have other risk factors for intrapartum GBS colonization.

• #51 Group B Streptococcus | Article | GLOWM

  https://www.glowm.com/article/heading/vol-17–maternal-immunization–group-b-streptococcus/id/418093

  EO-GBS infection may occur intrapartum by inhalation of the GBS bacteria as the infant passes through the birth canal or ascending transmission following premature rupture of the mothers membranes prior to labor. The GBS is then able to multiply in the amniotic fluid and colonize the fetal skin and mucous membranes. GBS is also able to cross the placental barrier, and can cause placental dysfunction. […] Transmission of LO-GBS disease is still incompletely understood but may occur after exposure to a high bacterial load, such as in breast milk, or via endogenous translocation in a colonized infant. […] GBS has several virulence factors that could be potential vaccine candidates. One of the most well-studied virulence factors of GBS is the capsular polysaccharide (CPS). GBS expresses 10 types of CPS, 97% of invasive isolates in all geographical regions are caused by serotypes Ia, Ib, II, III, and IV.

• #52 Group B Streptococcus | Article | GLOWM

  https://www.glowm.com/article/heading/vol-17–maternal-immunization–group-b-streptococcus/id/418093

  CPS-conjugate vaccines are being extensively studied; however, several drawbacks are limiting further advances. For instance, representative data regarding GBS invasive and colonizing serotypes from many LMIC are lacking, creating further obstacles to estimating vaccine efficacy in those regions where the disease burden is highest. Additionally, there is potential immune interference with other types of conjugate vaccines such as Haemophilus influenzae type b, meningococcal and pneumococcal conjugate vaccines, this may be due to carrier proteins used in developing conjugated vaccines such as CRM197 and tetanus toxoid.

• #53 Immune Responses to Invasive Group B Streptococcal Disease in Adults – Volume 22, Number 11—November 2016 – Emerging Infectious Diseases journal – CDC

  https://wwwnc.cdc.gov/eid/article/22/11/16-0914_article

  Immunization of nonpregnant adults could help prevent invasive group B Streptococcus (GBS) infections, but adult immune responses have not been investigated. […] The emergence of serotype V in the 1990s was first noted among GBS isolates from nonpregnant adults. […] Most GBS isolates can be assigned to a small number of CCs, including CC1, CC10, CC17, CC19, and CC23. […] All strains isolated from the patients reported here expressed CPS, pili, or both surface-associated GBS virulence factors. […] Our findings add to limited data regarding GBS virulence factors critical to invasive disease pathogenesis in adults. […] A significant increase in CPS-specific IgG was observed during the convalescent phase for each of the 6 GBS types causing invasive disease in these 87 patients. […] The concept that CPS-protein conjugate vaccines are immunogenic in older adults also is well established. […] Theoretically, a GBS conjugate CPS vaccine also incorporating pilus protein surface antigens could elicit a protective immune response providing protection for those adults at risk for invasive infection.

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