Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>

ABSTRACT Strains of emm89 Streptococcus pyogenes have become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125 emm89 strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. E...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Luchang Zhu, Randall J. Olsen, Waleed Nasser, Ivan de la Riva Morales, James M. Musser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fc90050479464179993c9577968831c0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fc90050479464179993c9577968831c0
record_format	dspace
spelling	oai:doaj.org-article:fc90050479464179993c9577968831c02021-11-15T15:41:30ZTrading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>10.1128/mBio.01378-152150-7511https://doaj.org/article/fc90050479464179993c9577968831c02015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01378-15https://doaj.org/toc/2150-7511ABSTRACT Strains of emm89 Streptococcus pyogenes have become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125 emm89 strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3 nga promoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S. pyogenes NADase) and SLO (streptolysin O). Second, all clade 3 strains lack the hasABC locus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report that emm89 strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3 emm89 S. pyogenes. IMPORTANCE S. pyogenes (group A streptococcus [GAS]) causes pharyngitis (“strep throat”), necrotizing fasciitis, and other human infections. Serious infections caused by emm89 S. pyogenes strains have recently increased in frequency in many countries. Based on whole-genome sequence analysis of 1,125 strains recovered from patients on two continents, we discovered that a new emm89 clone, termed clade 3, has two distinct genetic features compared to its predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid capsule virulence factor and (ii) increased production of the secreted cytolytic toxins SPN and SLO. emm89 S. pyogenes strains with the clade 3 phenotype (absence of capsule and high expression of SPN and SLO) are highly virulent in mice. These findings provide new understanding of how new virulent clones emerge and cause severe infections worldwide. This newfound knowledge of S. pyogenes virulence can be used to help understand future epidemics and conduct new translational research.Luchang ZhuRandall J. OlsenWaleed NasserIvan de la Riva MoralesJames M. MusserAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Luchang Zhu Randall J. Olsen Waleed Nasser Ivan de la Riva Morales James M. Musser Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
description	ABSTRACT Strains of emm89 Streptococcus pyogenes have become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125 emm89 strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3 nga promoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S. pyogenes NADase) and SLO (streptolysin O). Second, all clade 3 strains lack the hasABC locus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report that emm89 strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3 emm89 S. pyogenes. IMPORTANCE S. pyogenes (group A streptococcus [GAS]) causes pharyngitis (“strep throat”), necrotizing fasciitis, and other human infections. Serious infections caused by emm89 S. pyogenes strains have recently increased in frequency in many countries. Based on whole-genome sequence analysis of 1,125 strains recovered from patients on two continents, we discovered that a new emm89 clone, termed clade 3, has two distinct genetic features compared to its predecessors: (i) absence of the genes encoding antiphagocytic hyaluronic acid capsule virulence factor and (ii) increased production of the secreted cytolytic toxins SPN and SLO. emm89 S. pyogenes strains with the clade 3 phenotype (absence of capsule and high expression of SPN and SLO) are highly virulent in mice. These findings provide new understanding of how new virulent clones emerge and cause severe infections worldwide. This newfound knowledge of S. pyogenes virulence can be used to help understand future epidemics and conduct new translational research.
format	article
author	Luchang Zhu Randall J. Olsen Waleed Nasser Ivan de la Riva Morales James M. Musser
author_facet	Luchang Zhu Randall J. Olsen Waleed Nasser Ivan de la Riva Morales James M. Musser
author_sort	Luchang Zhu
title	Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_short	Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_full	Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_fullStr	Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_full_unstemmed	Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>
title_sort	trading capsule for increased cytotoxin production: contribution to virulence of a newly emerged clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">streptococcus pyogenes</named-content>
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/fc90050479464179993c9577968831c0
work_keys_str_mv	AT luchangzhu tradingcapsuleforincreasedcytotoxinproductioncontributiontovirulenceofanewlyemergedcladeofitalictoggleyesemm89italicnamedcontentcontenttypegenusspeciesstreptococcuspyogenesnamedcontent AT randalljolsen tradingcapsuleforincreasedcytotoxinproductioncontributiontovirulenceofanewlyemergedcladeofitalictoggleyesemm89italicnamedcontentcontenttypegenusspeciesstreptococcuspyogenesnamedcontent AT waleednasser tradingcapsuleforincreasedcytotoxinproductioncontributiontovirulenceofanewlyemergedcladeofitalictoggleyesemm89italicnamedcontentcontenttypegenusspeciesstreptococcuspyogenesnamedcontent AT ivandelarivamorales tradingcapsuleforincreasedcytotoxinproductioncontributiontovirulenceofanewlyemergedcladeofitalictoggleyesemm89italicnamedcontentcontenttypegenusspeciesstreptococcuspyogenesnamedcontent AT jamesmmusser tradingcapsuleforincreasedcytotoxinproductioncontributiontovirulenceofanewlyemergedcladeofitalictoggleyesemm89italicnamedcontentcontenttypegenusspeciesstreptococcuspyogenesnamedcontent
_version_	1718427743277809664

Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of <italic toggle="yes">emm89</italic> <named-content content-type="genus-species">Streptococcus pyogenes</named-content>

Ejemplares similares