Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins

ABSTRACT The core Mga (multiple gene activator) regulon of group A Streptococcus (GAS) contains genes encoding proteins involved in adhesion and immune evasion. While all GAS genomes contain genes for Mga and C5a peptidase, the intervening genes encoding M and M-like proteins vary between strains. T...

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Autores principales:	Hannah R. Frost, Mark R. Davies, Valérie Delforge, Dalila Lakhloufi, Martina Sanderson-Smith, Velusamy Srinivasan, Andrew C. Steer, Mark J. Walker, Bernard Beall, Anne Botteaux, Pierre R. Smeesters
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Streptococcus pyogenes Mga regulon M-like proteins global GAS diversity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/78a3ec1cbe8049a9b9e21594bb4641e9
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spelling	oai:doaj.org-article:78a3ec1cbe8049a9b9e21594bb4641e92021-11-15T15:27:53ZAnalysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins10.1128/mSphere.00806-192379-5042https://doaj.org/article/78a3ec1cbe8049a9b9e21594bb4641e92020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00806-19https://doaj.org/toc/2379-5042ABSTRACT The core Mga (multiple gene activator) regulon of group A Streptococcus (GAS) contains genes encoding proteins involved in adhesion and immune evasion. While all GAS genomes contain genes for Mga and C5a peptidase, the intervening genes encoding M and M-like proteins vary between strains. The genetic make-up of the Mga regulon of GAS was characterized by utilizing a collection of 1,688 GAS genomes that are representative of the global GAS population. Sequence variations were examined with multiple alignments, and the expression of all core Mga regulon genes was examined by quantitative reverse transcription-PCR in a representative strain collection. In 85.2% of the sampled genomes, the Mga locus contained genes encoding Mga, Mrp, M, Enn, and C5a peptidase proteins. These isolates account for 53% of global infections. Only 9.1% of genomes did not contain either an mrp or an enn gene. The pairwise identity within Enn (68.6%) and Mrp (83.2%) protein sequences was higher than within M proteins (44.7%). Gene expression varied between strains tested, but high expression was recorded for all genes in at least one strain. Previous nomenclature issues were clarified with molecular gene definitions. Our findings support a shift in focus in the GAS research field to further consider the role of Mrp and Enn in virulence and vaccine development. IMPORTANCE While the GAS M protein has been the leading vaccine target for decades, the bacteria encode many other virulence factors of interest for vaccine development. In this work, we show that emm-like genes are encoded in a remarkable majority of GAS genomes and expressed at a level similar to that for the emm gene. In collaboration with the U.S. Centers for Disease Control, we developed molecular definitions of the different emm and emm-like gene families. This clarification should abrogate mistyping of strains, especially in the area of whole-genome typing. We have also updated the emm-typing collection by removing emm-like gene sequences and provided in-depth analysis of Mrp and Enn protein sequence structure and diversity.Hannah R. FrostMark R. DaviesValérie DelforgeDalila LakhloufiMartina Sanderson-SmithVelusamy SrinivasanAndrew C. SteerMark J. WalkerBernard BeallAnne BotteauxPierre R. SmeestersAmerican Society for MicrobiologyarticleStreptococcus pyogenesMga regulonM-like proteinsglobal GAS diversityMicrobiologyQR1-502ENmSphere, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pyogenes Mga regulon M-like proteins global GAS diversity Microbiology QR1-502
spellingShingle	Streptococcus pyogenes Mga regulon M-like proteins global GAS diversity Microbiology QR1-502 Hannah R. Frost Mark R. Davies Valérie Delforge Dalila Lakhloufi Martina Sanderson-Smith Velusamy Srinivasan Andrew C. Steer Mark J. Walker Bernard Beall Anne Botteaux Pierre R. Smeesters Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins
description	ABSTRACT The core Mga (multiple gene activator) regulon of group A Streptococcus (GAS) contains genes encoding proteins involved in adhesion and immune evasion. While all GAS genomes contain genes for Mga and C5a peptidase, the intervening genes encoding M and M-like proteins vary between strains. The genetic make-up of the Mga regulon of GAS was characterized by utilizing a collection of 1,688 GAS genomes that are representative of the global GAS population. Sequence variations were examined with multiple alignments, and the expression of all core Mga regulon genes was examined by quantitative reverse transcription-PCR in a representative strain collection. In 85.2% of the sampled genomes, the Mga locus contained genes encoding Mga, Mrp, M, Enn, and C5a peptidase proteins. These isolates account for 53% of global infections. Only 9.1% of genomes did not contain either an mrp or an enn gene. The pairwise identity within Enn (68.6%) and Mrp (83.2%) protein sequences was higher than within M proteins (44.7%). Gene expression varied between strains tested, but high expression was recorded for all genes in at least one strain. Previous nomenclature issues were clarified with molecular gene definitions. Our findings support a shift in focus in the GAS research field to further consider the role of Mrp and Enn in virulence and vaccine development. IMPORTANCE While the GAS M protein has been the leading vaccine target for decades, the bacteria encode many other virulence factors of interest for vaccine development. In this work, we show that emm-like genes are encoded in a remarkable majority of GAS genomes and expressed at a level similar to that for the emm gene. In collaboration with the U.S. Centers for Disease Control, we developed molecular definitions of the different emm and emm-like gene families. This clarification should abrogate mistyping of strains, especially in the area of whole-genome typing. We have also updated the emm-typing collection by removing emm-like gene sequences and provided in-depth analysis of Mrp and Enn protein sequence structure and diversity.
format	article
author	Hannah R. Frost Mark R. Davies Valérie Delforge Dalila Lakhloufi Martina Sanderson-Smith Velusamy Srinivasan Andrew C. Steer Mark J. Walker Bernard Beall Anne Botteaux Pierre R. Smeesters
author_facet	Hannah R. Frost Mark R. Davies Valérie Delforge Dalila Lakhloufi Martina Sanderson-Smith Velusamy Srinivasan Andrew C. Steer Mark J. Walker Bernard Beall Anne Botteaux Pierre R. Smeesters
author_sort	Hannah R. Frost
title	Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins
title_short	Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins
title_full	Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins
title_fullStr	Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins
title_full_unstemmed	Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins
title_sort	analysis of global collection of group a <italic toggle="yes">streptococcus</italic> genomes reveals that the majority encode a trio of m and m-like proteins
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/78a3ec1cbe8049a9b9e21594bb4641e9
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Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like Proteins

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