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Nonimmune antibody interactions of Group A Streptococcus M and M-like proteins.

ABSTRACT: M and M-like proteins are major virulence factors of the widespread and potentially deadly bacterial pathogen Streptococcus pyogenes. These proteins confer resistance against innate and adaptive immune responses by recruiting specific human proteins to the streptococcal surface. Nonimmune recruitment of immunoglobulins G (IgG) and A (IgA) through their fragment crystallizable (Fc) domains by M and M-like proteins was described almost 40 years ago, but its impact on virulence remains unresolved. These interactions have been suggested to be consequential under immune conditions at mucosal surfaces and in secretions but not in plasma, while other evidence suggests importance in evading phagocytic killing in nonimmune blood. Recently, an indirect effect of Fc-binding through ligand-induced stabilization of an M-like protein was shown to increase virulence. Nonimmune recruitment has also been seen to contribute to tissue damage in animal models of autoimmune diseases triggered by S. pyogenes infection. The damage was treatable by targeting Fc-binding. This and other potential therapeutic applications warrant renewed attention to Fc-binding by M and M-like proteins.

SUBMITTER: Mills JO

PROVIDER: S-EPMC7906336 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Nonimmune antibody interactions of Group A Streptococcus M and M-like proteins.

Mills Jori O JO Ghosh Partho P

PLoS pathogens 20210225 2

M and M-like proteins are major virulence factors of the widespread and potentially deadly bacterial pathogen Streptococcus pyogenes. These proteins confer resistance against innate and adaptive immune responses by recruiting specific human proteins to the streptococcal surface. Nonimmune recruitment of immunoglobulins G (IgG) and A (IgA) through their fragment crystallizable (Fc) domains by M and M-like proteins was described almost 40 years ago, but its impact on virulence remains unresolved. ...[more]

PMID: 33630944

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Project description:BackgroundStreptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of life-threatening neonatal meningitis and survivors often suffer permanent neurological damage. How this organism interacts with the meninges and subsequently with astrocytes that constitute the underlying cortical glia limitans superficialis is not known.Methodology/principal findingsIn this paper, we demonstrate dose-dependent adherence of GBS over time to human meningioma cells and fetal astrocytes in vitro, which was not influenced by expression of either ?-haemolysin/cytolysin (?-h/c) toxin, different capsule serotypes or by absence of capsule (p>0.05). Internalization of GBS by both cell types was, however, a slow and an infrequent event (only 0.02-0.4% of associated bacteria were internalised by 9 h). Expression of ?-h/c toxin did not play a role in invasion (p>0.05), whereas capsule expression lead to a reduction (p<0.05) in the numbers of intracellular bacteria recovered. GBS strains induced cytotoxicity as demonstrated by the measurement of lactate dehydrogenase (LDH) enzyme release by 9 h and by viable staining. Increasing levels of meningioma cell death correlated with bacterial growth and the phenotype of ?-h/c toxin production, i.e. from weakly, to normo- to hyper-haemolytic. However, cytotoxicity was significantly greater (p<0.05) towards astrocytes, and infection with initial MOI?0.003 induced 70-100% LDH release. By comparing wild-type (?-h/c(+)) and mutant (?cylE ?-h/c(-)) strains and ?-h/c toxin extracts and by using the surfactant dipalmitoylphosphatidylcholine in cytotoxicity inhibition experiments, ?-h/c toxin was demonstrated as principally responsible for cell death.Conclusions/significanceThis study has described key events in the interactions of GBS with meningeal cells and astrocytes in vitro and a major virulence role for ?-h/c toxin. Understanding the mechanisms involved will help to identify potential therapies for improving patient survival and for reducing the incidence and severity of neurological sequelae.

Dataset Information

Nonimmune antibody interactions of Group A Streptococcus M and M-like proteins.

Publications

Nonimmune antibody interactions of Group A Streptococcus M and M-like proteins.

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