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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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-02-01
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| Series: | mSphere |
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| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00806-19 |
| _version_ | 1818427853413285888 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:52:20Z |
| format | Article |
| id | doaj.art-78a3ec1cbe8049a9b9e21594bb4641e9 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-14T14:52:20Z |
| publishDate | 2020-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-78a3ec1cbe8049a9b9e21594bb4641e92022-12-21T22:57:05ZengAmerican Society for MicrobiologymSphere2379-50422020-02-015110.1128/mSphere.00806-19Analysis of Global Collection of Group A <italic toggle="yes">Streptococcus</italic> Genomes Reveals that the Majority Encode a Trio of M and M-Like ProteinsHannah R. Frost0Mark R. Davies1Valérie Delforge2Dalila Lakhloufi3Martina Sanderson-Smith4Velusamy Srinivasan5Andrew C. Steer6Mark J. Walker7Bernard Beall8Anne Botteaux9Pierre R. Smeesters10Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, AustraliaMolecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, BelgiumMolecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, BelgiumIllawarra Health and Medical Research Institute and Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, AustraliaNational Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USATropical Diseases Research Group, Murdoch Children’s Research Institute, Melbourne, AustraliaAustralian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, AustraliaNational Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USAMolecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, BelgiumMolecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, BelgiumABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00806-19Streptococcus pyogenesMga regulonM-like proteinsglobal GAS diversity |
| spellingShingle | 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 mSphere Streptococcus pyogenes Mga regulon M-like proteins global GAS diversity |
| 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_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_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_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 |
| topic | Streptococcus pyogenes Mga regulon M-like proteins global GAS diversity |
| url | https://journals.asm.org/doi/10.1128/mSphere.00806-19 |
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