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A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins
Streptococcus equi subspecies zooepidemicus (SEZ) are group C streptococci that are important pathogens of economically valuable animals such as horses and pigs. Here, we found that many SEZ isolates bind to a monoclonal antibody that recognizes poly-N-acetylglucosamine (PNAG), a polymer that is fou...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805998/ https://www.ncbi.nlm.nih.gov/pubmed/31641092 http://dx.doi.org/10.1128/mBio.02500-19 |
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author | D’Gama, Jonathan D. Ma, Zhe Zhang, Hailong Liu, Xu Fan, Hongjie Morris, Ellen Ruth A. Cohen, Noah D. Cywes-Bentley, Colette Pier, Gerald B. Waldor, Matthew K. |
author_facet | D’Gama, Jonathan D. Ma, Zhe Zhang, Hailong Liu, Xu Fan, Hongjie Morris, Ellen Ruth A. Cohen, Noah D. Cywes-Bentley, Colette Pier, Gerald B. Waldor, Matthew K. |
author_sort | D’Gama, Jonathan D. |
collection | PubMed |
description | Streptococcus equi subspecies zooepidemicus (SEZ) are group C streptococci that are important pathogens of economically valuable animals such as horses and pigs. Here, we found that many SEZ isolates bind to a monoclonal antibody that recognizes poly-N-acetylglucosamine (PNAG), a polymer that is found as a surface capsule-like structure on diverse microbes. A fluorescence-activated cell sorting-based transposon insertion sequencing (Tn-seq) screen, coupled with whole-genome sequencing, was used to search for genes for PNAG biosynthesis. Surprisingly, mutations in a gene encoding an M-like protein, szM, and the adjacent transcription factor, designated sezV, rendered strains PNAG negative. SezV was required for szM expression and transcriptome analysis showed that SezV has a small regulon. SEZ strains with inactivating mutations in either sezV or szM were highly attenuated in a mouse model of infection. Comparative genomic analyses revealed that linked sezV and szM homologues are present in all SEZ, S. equi subspecies equi (SEE), and M18 group A streptococcal (GAS) genomes in the database, but not in other streptococci. The antibody to PNAG bound to a wide range of SEZ, SEE, and M18 GAS strains. Immunochemical studies suggest that the SzM protein may be decorated with a PNAG-like oligosaccharide although an intact oligosaccharide substituent could not be isolated. Collectively, our findings suggest that the szM and sezV loci define a subtype of virulent streptococci and that an antibody to PNAG may have therapeutic applications in animal and human diseases caused by streptococci bearing SzM-like proteins. |
format | Online Article Text |
id | pubmed-6805998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-68059982019-10-28 A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins D’Gama, Jonathan D. Ma, Zhe Zhang, Hailong Liu, Xu Fan, Hongjie Morris, Ellen Ruth A. Cohen, Noah D. Cywes-Bentley, Colette Pier, Gerald B. Waldor, Matthew K. mBio Research Article Streptococcus equi subspecies zooepidemicus (SEZ) are group C streptococci that are important pathogens of economically valuable animals such as horses and pigs. Here, we found that many SEZ isolates bind to a monoclonal antibody that recognizes poly-N-acetylglucosamine (PNAG), a polymer that is found as a surface capsule-like structure on diverse microbes. A fluorescence-activated cell sorting-based transposon insertion sequencing (Tn-seq) screen, coupled with whole-genome sequencing, was used to search for genes for PNAG biosynthesis. Surprisingly, mutations in a gene encoding an M-like protein, szM, and the adjacent transcription factor, designated sezV, rendered strains PNAG negative. SezV was required for szM expression and transcriptome analysis showed that SezV has a small regulon. SEZ strains with inactivating mutations in either sezV or szM were highly attenuated in a mouse model of infection. Comparative genomic analyses revealed that linked sezV and szM homologues are present in all SEZ, S. equi subspecies equi (SEE), and M18 group A streptococcal (GAS) genomes in the database, but not in other streptococci. The antibody to PNAG bound to a wide range of SEZ, SEE, and M18 GAS strains. Immunochemical studies suggest that the SzM protein may be decorated with a PNAG-like oligosaccharide although an intact oligosaccharide substituent could not be isolated. Collectively, our findings suggest that the szM and sezV loci define a subtype of virulent streptococci and that an antibody to PNAG may have therapeutic applications in animal and human diseases caused by streptococci bearing SzM-like proteins. American Society for Microbiology 2019-10-22 /pmc/articles/PMC6805998/ /pubmed/31641092 http://dx.doi.org/10.1128/mBio.02500-19 Text en Copyright © 2019 D’Gama et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article D’Gama, Jonathan D. Ma, Zhe Zhang, Hailong Liu, Xu Fan, Hongjie Morris, Ellen Ruth A. Cohen, Noah D. Cywes-Bentley, Colette Pier, Gerald B. Waldor, Matthew K. A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins |
title | A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins |
title_full | A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins |
title_fullStr | A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins |
title_full_unstemmed | A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins |
title_short | A Conserved Streptococcal Virulence Regulator Controls the Expression of a Distinct Class of M-Like Proteins |
title_sort | conserved streptococcal virulence regulator controls the expression of a distinct class of m-like proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805998/ https://www.ncbi.nlm.nih.gov/pubmed/31641092 http://dx.doi.org/10.1128/mBio.02500-19 |
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