Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>

ABSTRACT Populations of a bacterial pathogen, whether recovered from a single patient or from a worldwide study, are often a heterogeneous mix of genetically and phenotypically divergent strains. Such heterogeneity is of value in changing environments and arises via mechanisms such as gene gain or g...

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Autores principales:	Poulomee Sarkar, Jessica L. Danger, Ira Jain, Laura A. Meadows, Christopher Beam, Josette Medicielo, Cameron Burgess, James M. Musser, Paul Sumby
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Streptococcus pyogenes gene mutation gene regulation phenotypic variation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/df3136ebea0b42d1bef0975929d58596
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spelling	oai:doaj.org-article:df3136ebea0b42d1bef0975929d585962021-11-15T15:22:26ZPhenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>10.1128/mSphere.00519-182379-5042https://doaj.org/article/df3136ebea0b42d1bef0975929d585962018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00519-18https://doaj.org/toc/2379-5042ABSTRACT Populations of a bacterial pathogen, whether recovered from a single patient or from a worldwide study, are often a heterogeneous mix of genetically and phenotypically divergent strains. Such heterogeneity is of value in changing environments and arises via mechanisms such as gene gain or gene mutation. Here, we identify an isolate of serotype M12 group A Streptococcus (GAS) (Streptococcus pyogenes) that has a natural mutation in rocA, which encodes an accessory protein to the virulence-regulating two-component system CovR/CovS (CovR/S). Disruption of RocA activity results in the differential expression of multiple GAS virulence factors, including the anti-phagocytic hyaluronic acid capsule and the chemokine protease SpyCEP. While some of our data regarding RocA-regulated genes overlaps with previous studies, which were performed with isolates of alternate GAS serotypes, some variability was also observed. Perhaps as a consequence of this alternate regulatory activity, we discovered that the contribution of RocA to the ability of the M12 isolate to survive and proliferate in human blood ex vivo is opposite that previously observed in M1, M3, and M18 GAS strains. Specifically, rocA mutation reduced, rather than enhanced, survival of the isolate. Finally, we also present data from an analysis of rocA transcription and show that rocA is transcribed in both mono- and polycistronic mRNAs. In aggregate, our data provide insight into the important regulatory role of RocA and into the mechanisms and consequences of GAS phenotypic heterogeneity. IMPORTANCE This study investigates the regulatory and phenotypic consequences of a naturally occurring mutation in a strain of the bacterial pathogen the group A Streptococcus (Streptococcus pyogenes). We show that this mutation, which occurs in a regulator-encoding gene, rocA, leads to altered virulence factor expression and reduces the ability of this isolate to survive in human blood. Critically, the blood survival phenotype and the assortment of genes regulated by RocA differ compared to previous studies into RocA activity. The data are consistent with there being strain- or serotype-specific variability in RocA function. Given that phenotypic variants can lead to treatment failures and escape from preventative regimes, our data provide information with regard to a mechanism of phenotypic variation in a prevalent Gram-positive pathogen.Poulomee SarkarJessica L. DangerIra JainLaura A. MeadowsChristopher BeamJosette MedicieloCameron BurgessJames M. MusserPaul SumbyAmerican Society for MicrobiologyarticleStreptococcus pyogenesgene mutationgene regulationphenotypic variationMicrobiologyQR1-502ENmSphere, Vol 3, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pyogenes gene mutation gene regulation phenotypic variation Microbiology QR1-502
spellingShingle	Streptococcus pyogenes gene mutation gene regulation phenotypic variation Microbiology QR1-502 Poulomee Sarkar Jessica L. Danger Ira Jain Laura A. Meadows Christopher Beam Josette Medicielo Cameron Burgess James M. Musser Paul Sumby Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>
description	ABSTRACT Populations of a bacterial pathogen, whether recovered from a single patient or from a worldwide study, are often a heterogeneous mix of genetically and phenotypically divergent strains. Such heterogeneity is of value in changing environments and arises via mechanisms such as gene gain or gene mutation. Here, we identify an isolate of serotype M12 group A Streptococcus (GAS) (Streptococcus pyogenes) that has a natural mutation in rocA, which encodes an accessory protein to the virulence-regulating two-component system CovR/CovS (CovR/S). Disruption of RocA activity results in the differential expression of multiple GAS virulence factors, including the anti-phagocytic hyaluronic acid capsule and the chemokine protease SpyCEP. While some of our data regarding RocA-regulated genes overlaps with previous studies, which were performed with isolates of alternate GAS serotypes, some variability was also observed. Perhaps as a consequence of this alternate regulatory activity, we discovered that the contribution of RocA to the ability of the M12 isolate to survive and proliferate in human blood ex vivo is opposite that previously observed in M1, M3, and M18 GAS strains. Specifically, rocA mutation reduced, rather than enhanced, survival of the isolate. Finally, we also present data from an analysis of rocA transcription and show that rocA is transcribed in both mono- and polycistronic mRNAs. In aggregate, our data provide insight into the important regulatory role of RocA and into the mechanisms and consequences of GAS phenotypic heterogeneity. IMPORTANCE This study investigates the regulatory and phenotypic consequences of a naturally occurring mutation in a strain of the bacterial pathogen the group A Streptococcus (Streptococcus pyogenes). We show that this mutation, which occurs in a regulator-encoding gene, rocA, leads to altered virulence factor expression and reduces the ability of this isolate to survive in human blood. Critically, the blood survival phenotype and the assortment of genes regulated by RocA differ compared to previous studies into RocA activity. The data are consistent with there being strain- or serotype-specific variability in RocA function. Given that phenotypic variants can lead to treatment failures and escape from preventative regimes, our data provide information with regard to a mechanism of phenotypic variation in a prevalent Gram-positive pathogen.
format	article
author	Poulomee Sarkar Jessica L. Danger Ira Jain Laura A. Meadows Christopher Beam Josette Medicielo Cameron Burgess James M. Musser Paul Sumby
author_facet	Poulomee Sarkar Jessica L. Danger Ira Jain Laura A. Meadows Christopher Beam Josette Medicielo Cameron Burgess James M. Musser Paul Sumby
author_sort	Poulomee Sarkar
title	Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>
title_short	Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>
title_full	Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>
title_fullStr	Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>
title_full_unstemmed	Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>
title_sort	phenotypic variation in the group a <italic toggle="yes">streptococcus</italic> due to natural mutation of the accessory protein-encoding gene <italic toggle="yes">roca</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/df3136ebea0b42d1bef0975929d58596
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Phenotypic Variation in the Group A <italic toggle="yes">Streptococcus</italic> Due to Natural Mutation of the Accessory Protein-Encoding Gene <italic toggle="yes">rocA</italic>

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