scholarly journals Distinct Group B Streptococcus sequence and capsule types differentially impact macrophage stress and inflammatory signaling responses

2021 ◽  
Author(s):  
Rebecca A. Flaherty ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy ◽  
Margaret G. Petroff ◽  
Shannon D. Manning
Keyword(s):  
Cell Death ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Distinct Group ◽  
Innate Immune Responses ◽  
Inflammatory Signaling ◽  
Phenotypic Differences ◽  
Pathway Activation ◽  
Nfκb Pathway ◽  
Group B

Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that can contribute to the induction of preterm birth in colonized pregnant women and to severe neonatal disease. Many questions regarding the mechanisms that drive GBS-associated pathogenesis remain unanswered, and it is not yet clear why virulence has been observed to vary so extensively across GBS strains. Previously, we demonstrated that GBS strains of different sequence types (STs) and capsule (CPS) types induce different cytokine profiles in infected THP-1 macrophage-like cells. Here, we have expanded on these studies by utilizing the same set of genetically diverse GBS isolates to assess ST and CPS-specific differences in upstream cell death and inflammatory signaling pathways. Our results demonstrate that particularly virulent STs and CPS types, such as the ST-17 and CPS III groups, induce enhanced JNK and NFκB pathway activation following GBS infection of macrophages when compared with other ST or CPS groups. Additionally, we found that ST-17, CPS III and CPS V GBS strains induce the greatest levels of macrophage cell death during infection and exhibit a more pronounced ability to be internalized and to survive in macrophages following phagocytosis. These data provide further support for the hypothesis that variable host innate immune responses to GBS, which significantly impact pathogenesis, stem in part from genotypic and phenotypic differences among GBS isolates. These and similar studies may inform the development of improved diagnostic, preventive, or therapeutic strategies targeting invasive GBS infections.

Childhood meningitis in the conjugate vaccine era: a prospective cohort study

2014 ◽  
Vol 100 (3) ◽  
pp. 292-294 ◽  
Author(s):  
Manish Sadarangani ◽  
Louise Willis ◽  
Seilesh Kadambari ◽  
Stuart Gormley ◽  
Zoe Young ◽  
...  
Keyword(s):  
Bacterial Meningitis ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Antibiotic Use ◽  
Viral Meningitis ◽  
Older Children ◽  
C Reactive Protein ◽  
Blood Cell Count ◽  
Reactive Protein ◽  
Group B

Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis—13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.

scholarly journals ZBP1 induces inflammatory signaling via RIPK3 and promotes SARS-CoV-2-induced cytokine expression

2021 ◽  
Author(s):  
Ruoshi Peng ◽  
Xuan Wang-Kan ◽  
Manja Idorn ◽  
Felix Y Zhou ◽  
Susana L Orozco ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Kinase Activity ◽  
Caspase 8 ◽  
Dependent Manner ◽  
Innate Immune Responses ◽  
Inflammatory Signaling ◽  
Antiviral Responses ◽  
Nucleic Acid Sensor ◽  
Activity Dependent

AbstractCOVID-19 caused by the SARS-CoV-2 virus remains a threat to global health. The disease severity is mediated by cell death and inflammation, which regulate both the antiviral and the pathological innate immune responses. ZBP1, an interferon-induced cytosolic nucleic acid sensor, facilitates antiviral responses via RIPK3. Although ZBP1-mediated cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway that depends on ubiquitination and RIPK3’s scaffolding ability independently of cell death. In human cells, ZBP1 associates with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. RIPK1 and ZBP1 are ubiquitinated to promote TAK1- and IKK-mediated inflammatory signaling. Additionally, RIPK1 recruits the p43/41-caspase-8-p43-FLIP heterodimer to suppress RIPK3 kinase activity, which otherwise promotes inflammatory signaling in a kinase activity-dependent manner. Lastly, we show that ZBP1 contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK1-RIPK3-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspase-8. Our results suggest the ZBP1 pathway contributes to inflammation in response to SARS-CoV-2 infection.

Uvaol effects in Group B Streptococcus-induced trophoblast cell death and inflammation

Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e40-e41
Author(s):  
Rayane M. Botelho ◽  
Liliane Patricia G. Tenorio ◽  
Ana Lucia M. Silva ◽  
Eloisa L.L. Tanabe ◽  
keyla S.N. Pires ◽  
...  
Keyword(s):  
Cell Death ◽  
Group B Streptococcus ◽  
Trophoblast Cell ◽  
Group B

scholarly journals Modulation of Death and Inflammatory Signaling in Decidual Stromal Cells following Exposure to Group B Streptococcus

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Rebecca A. Flaherty ◽  
Maja Magel ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy ◽  
Margaret G. Petroff ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Mitogen Activated Protein Kinase ◽  
Antibody Microarray ◽  
Endometrial Stromal Cells ◽  
Decidual Tissue ◽  
Group B

ABSTRACT Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that contributes to miscarriage, preterm birth, and serious neonatal infections. Studies have indicated that some multilocus sequence types (STs) of GBS are more likely to cause severe disease than others. We hypothesized that the ability of GBS to elicit varying host responses in maternal decidual tissue during pregnancy is an important factor regulating infection and disease severity. To address this hypothesis, we utilized an antibody microarray to compare changes in production and activation of host signaling proteins in decidualized telomerase-immortalized human endometrial stromal cells (dT-HESCs) following infection with GBS strains from septic neonates or colonized mothers. GBS infection increased levels of total and phosphorylated mitogen-activated protein kinase (MAPK) family members such as p38 and JNK and induced nuclear factor kappa B (NF-κB) pathway activation. Infection also altered the regulation of additional proteins that mediate cell death and inflammation in a strain-specific manner, which could be due to the observed variation in attachment to and invasion of the decidual stromal cells and ability to lyse red blood cells. Further analyses confirmed array results and revealed that p38 promotes programmed necrosis in dT-HESCs. Together, the observed signaling changes may contribute to deregulation of critical developmental signaling cascades and inflammatory responses following infection, both of which could trigger GBS-associated pregnancy complications.

scholarly journals Prevalence, serotype and antibiotic susceptibility of Group B Streptococcus isolated from pregnant women in Jakarta, Indonesia

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252328
Author(s):  
Dodi Safari ◽  
Septiani Madonna Gultom ◽  
Wisnu Tafroji ◽  
Athiya Azzahidah ◽  
Frida Soesanti ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Antibiotic Susceptibility ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Neonatal Infection ◽  
Multidrug Resistant ◽  
Latex Agglutination ◽  
Antimicrobial Susceptibility Profile ◽  
Culture Identification ◽  
Group B

Group B Streptococcus (GBS) is a bacterial pathogen which is a leading cause of neonatal infection. Currently, there are limited GBS data available from the Indonesian population. In this study, GBS colonization, serotype distribution and antimicrobial susceptibility profile of isolates were investigated among pregnant women in Jakarta, Indonesia. Demographics data, clinical characteristics and vaginal swabs were collected from 177 pregnant women (mean aged: 28.7 years old) at 29–40 weeks of gestation. Bacterial culture identification tests and latex agglutination were performed for GBS. Serotyping was done by conventional multiplex PCR and antibiotic susceptibility testing by broth microdilution. GBS colonization was found in 53 (30%) pregnant women. Serotype II was the most common serotype (30%) followed by serotype III (23%), Ia and IV (13% each), VI (8%), Ib and V (6% each), and one non-typeable strain. All isolates were susceptible to vancomycin, penicillin, ampicillin, cefotaxime, daptomycin and linezolid. The majority of GBS were resistant to tetracycline (89%) followed by clindamycin (21%), erythromycin (19%), and levofloxacin (6%). The serotype III was more resistant to erythromycin, clindamycin, and levofloxacin and these isolates were more likely to be multidrug resistant (6 out of 10) compared to other serotypes. This report provides demographics of GBS colonization and isolate characterization in pregnant women in Indonesia. The results may facilitate preventive strategies to reduce neonatal GBS infection and improve its treatment.

scholarly journals The fall and rise of group B Streptococcus in dairy cattle: reintroduction due to human-to-cattle host jumps?

2021 ◽  
Author(s):  
Chiara Crestani ◽  
Taya L Forde ◽  
Samantha J Lycett ◽  
Mark A Holmes ◽  
Charlotta Fasth ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Tetracycline Resistance ◽  
Control Programs ◽  
Animal Disease Control ◽  
Long Read ◽  
Group B ◽  
Globally Distributed ◽  
Mastitis Control

Group B Streptococcus (GBS; Streptococcus agalactiae) is a major neonatal and opportunistic bacterial pathogen of humans and an important cause of mastitis in dairy cattle with significant impacts on food security. Following the introduction of mastitis control programs in the 1950s, GBS was nearly eradicated from the dairy industry in northern Europe, followed by re-emergence in the 21st century. Here, we sought to explain this re-emergence based on short and long read sequencing of historical (1953-1978; n = 44) and contemporary (1997-2012; n = 76) bovine GBS isolates. Our data show that a globally distributed bovine-associated lineage of GBS was commonly detected among historical isolates but never among contemporary isolates. By contrast, tetracycline resistance, which is present in all major GBS clones adapted to humans, was commonly and uniquely detected in contemporary bovine isolates. These observations provide evidence for strain replacement and suggest a human origin of newly emerged strains. Three novel GBS plasmids were identified, including two showing >98% homology with plasmids from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis, which co-exist with GBS in the human oropharynx. Our findings support introduction of GBS into the dairy population due to human-to-cattle jumps on multiple occasions and demonstrate that reverse zoonotic transmission can erase successes of animal disease control campaigns.

scholarly journals Genetically distinct Group B Streptococcus strains induce varying macrophage cytokine responses

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222910 ◽  
Author(s):  
Rebecca A. Flaherty ◽  
Elena C. Borges ◽  
Jessica A. Sutton ◽  
David M. Aronoff ◽  
Jennifer A. Gaddy ◽  
...  
Keyword(s):  
Group B Streptococcus ◽  
Distinct Group ◽  
Cytokine Responses ◽  
Group B ◽  
Macrophage Cytokine

scholarly journals The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus.

1980 ◽  
Vol 151 (5) ◽  
pp. 1275-1287 ◽  
Author(s):  
M S Edwards ◽  
A Nicholson-Weller ◽  
C J Baker ◽  
D L Kasper
Keyword(s):  
Sialic Acid ◽  
Specific Antibody ◽  
Alternative Pathway ◽  
Group B Streptococcus ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Pathway Activation ◽  
Alternative Complement ◽  
Group B

The native capsular polysaccharide antigen of type III, group B Streptococcus contains a terminal sialic acid residue on each repeating unit that masks all end-group galactopyranose residues and prevents alternative pathway complement activation by adult human sera in the absence of type-specific antibody. The critical role of the sialic acid residues in allowing the organism to evade activating the alternative complement pathway was shown when neuraminidase treatment of the organism converted the bacteria to activators of the alternative pathway as assessed in agammaglobulinemic serum. The requirement for specific antibody in permitting alternative pathway activation by the fully sialated bacteria was shown when sera that contained low levels of specific antibody failed to activate this pathway, and when prior absorption of serum that contained higher type-specific antibody levels with the capsular antigen failed to activate this pathway. The use of C2-deficient sera showed that the calssical pathway was not required for antibody-dependent alternative pathway activation. The use of isotonic, pH 7.5, veronal-NaCl buffer that contained 1% gelatin and that was supplemented to 4 mM Mg++ and 16 mM EGTA and adjusted to pH 7.5 (MgEGTA) ruled out the participation of the C1-bypass pathway. The presence of sialic acid on the bacterial surface is one means of evading an important mechanism of natural immunity, namely activation of complement by the alternative pathway. Only specific antibody, i.e., acquired immunity, can overcome this virulence factor.

scholarly journals Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3333-3336 ◽  
Author(s):  
Aaron F. Carlin ◽  
Satoshi Uchiyama ◽  
Yung-Chi Chang ◽  
Amanda L. Lewis ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Molecular Mimicry ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Extracellular Dna ◽  
Dependent Manner ◽  
Bacterial Survival ◽  
Amino Terminal ◽  
Group B ◽  
In Cis

Abstract Human neutrophil Siglec-9 is a lectin that recognizes sialic acids (Sias) via an amino-terminal V-set Ig domain and possesses tyrosine-based inhibitory motifs in its cytoplasmic tail. We hypothesized that Siglec-9 recognizes host Sias as “self,” including in cis interactions with Sias on the neutrophil's own surface, thereby dampening unwanted neutrophil reactivity. Here we show that neutrophils presented with immobilized multimerized Siaα2-3Galβ1-4GlcNAc units engage them in trans via Siglec-9. The sialylated capsular polysaccharide of group B Streptococcus (GBS) also presents terminal Siaα2-3Galβ1-4GlcNAc units, and similarly engages neutrophil Siglec-9, dampening neutrophil responses in a Sia- and Siglec-9–dependent manner. Reduction in the neutrophil oxidative burst, diminished formation of neutrophil extracellular DNA traps, and increased bacterial survival are also facilitated by GBS sialylated capsular polysaccharide interactions with Siglec-9. Thus, GBS can impair neutrophil defense functions by coopting a host inhibitory receptor via sialoglycan molecular mimicry, a novel mechanism of bacterial immune evasion.

scholarly journals The fall and rise of group B Streptococcus in dairy cattle: reintroduction due to human-to-cattle host jumps?

2021 ◽  
Vol 7 (9) ◽  
Author(s):  
Chiara Crestani ◽  
Taya L. Forde ◽  
Samantha J. Lycett ◽  
Mark A. Holmes ◽  
Charlotta Fasth ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Type Species ◽  
Sequence Similarity ◽  
Group B Streptococcus ◽  
Bacterial Pathogen ◽  
Tetracycline Resistance ◽  
Content Type ◽  
Link Type ◽  
Animal Disease Control ◽  
Group B

Group B Streptococcus (GBS; Streptococcus agalactiae ) is a major neonatal and opportunistic bacterial pathogen of humans and an important cause of mastitis in dairy cattle with significant impacts on food security. Following the introduction of mastitis control programmes in the 1950s, GBS was nearly eradicated from the dairy industry in northern Europe, followed by re-emergence in the 21st century. Here, we sought to explain this re-emergence based on short and long read sequencing of historical (1953–1978; n=44) and contemporary (1997–2012; n=76) bovine GBS isolates. Our data show that a globally distributed bovine-associated lineage of GBS was commonly detected among historical isolates but never among contemporary isolates. By contrast, tetracycline resistance, which is present in all major GBS clones adapted to humans, was commonly and uniquely detected in contemporary bovine isolates. These observations provide evidence for strain replacement and suggest a human origin of newly emerged strains. Three novel GBS plasmids were identified, including two showing >98 % sequence similarity with plasmids from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis , which co-exist with GBS in the human oropharynx. Our findings support introduction of GBS into the dairy population due to human-to-cattle jumps on multiple occasions and demonstrate that reverse zoonotic transmission can erase successes of animal disease control campaigns.

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