USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus

ABSTRACT The surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed against Staphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Susan Boyle-Vavra, Xue Li, Md Tauqeer Alam, Timothy D. Read, Julia Sieth, Colette Cywes-Bentley, Ginette Dobbins, Michael Z. David, Neha Kumar, Samantha J. Eells, Loren G. Miller, David J. Boxrud, Henry F. Chambers, Ruth Lynfield, Jean C. Lee, Robert S. Daum
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e53591632de24437be907d7162248af0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e53591632de24437be907d7162248af0
record_format	dspace
spelling	oai:doaj.org-article:e53591632de24437be907d7162248af02021-11-15T15:41:33ZUSA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus10.1128/mBio.02585-142150-7511https://doaj.org/article/e53591632de24437be907d7162248af02015-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02585-14https://doaj.org/toc/2150-7511ABSTRACT The surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed against Staphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistant S. aureus (MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptible S. aureus (MSSA) isolates were CP negative (CP−). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP−. Whole-genome sequence analysis of 146 CP− USA300 MRSA isolates revealed they all carry a cap5 locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in the cap5 promoter, cap5D nucleotide 994, and cap5E nucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same four cap5 mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of the cap loci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specific cap5 mutations arose sequentially in S. aureus in a common ancestor of USA300 and USA500 isolates. IMPORTANCE The USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP−) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP+) phenotype is unlikely in vivo or in vitro since it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP− and provide new insight into the evolution of the USA300 and USA500 lineages.Susan Boyle-VavraXue LiMd Tauqeer AlamTimothy D. ReadJulia SiethColette Cywes-BentleyGinette DobbinsMichael Z. DavidNeha KumarSamantha J. EellsLoren G. MillerDavid J. BoxrudHenry F. ChambersRuth LynfieldJean C. LeeRobert S. DaumAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 2 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Susan Boyle-Vavra Xue Li Md Tauqeer Alam Timothy D. Read Julia Sieth Colette Cywes-Bentley Ginette Dobbins Michael Z. David Neha Kumar Samantha J. Eells Loren G. Miller David J. Boxrud Henry F. Chambers Ruth Lynfield Jean C. Lee Robert S. Daum USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus
description	ABSTRACT The surface capsular polysaccharide (CP) is a virulence factor that has been used as an antigen in several successful vaccines against bacterial pathogens. A vaccine has not yet been licensed against Staphylococcus aureus, although two multicomponent vaccines that contain CP antigens are in clinical trials. In this study, we evaluated CP production in USA300 methicillin-resistant S. aureus (MRSA) isolates that have become the predominant community-associated MRSA clones in the United States. We found that all 167 USA300 MRSA and 50 USA300 methicillin-susceptible S. aureus (MSSA) isolates were CP negative (CP−). Moreover, all 16 USA500 isolates, which have been postulated to be the progenitor lineage of USA300, were also CP−. Whole-genome sequence analysis of 146 CP− USA300 MRSA isolates revealed they all carry a cap5 locus with 4 conserved mutations compared with strain Newman. Genetic complementation experiments revealed that three of these mutations (in the cap5 promoter, cap5D nucleotide 994, and cap5E nucleotide 223) ablated CP production in USA300 and that Cap5E75 Asp, located in the coenzyme-binding domain, is essential for capsule production. All but three USA300 MSSA isolates had the same four cap5 mutations found in USA300 MRSA isolates. Most isolates with a USA500 pulsotype carried three of these four USA300-specific mutations, suggesting the fourth mutation occurred in the USA300 lineage. Phylogenetic analysis of the cap loci of our USA300 isolates as well as publicly available genomes from 41 other sequence types revealed that the USA300-specific cap5 mutations arose sequentially in S. aureus in a common ancestor of USA300 and USA500 isolates. IMPORTANCE The USA300 MRSA clone emerged as a community-associated pathogen in the United States nearly 20 years ago. Since then, it has rapidly disseminated and now causes health care-associated infections. This study shows that the CP-negative (CP−) phenotype has persisted among USA300 isolates and is a universal and characteristic trait of this highly successful MRSA lineage. It is important to note that a vaccine consisting solely of CP antigens would not likely demonstrate high efficacy in the U.S. population, where about half of MRSA isolates comprise USA300. Moreover, conversion of a USA300 strain to a CP-positive (CP+) phenotype is unlikely in vivo or in vitro since it would require the reversion of 3 mutations. We have also established that USA300 MSSA isolates and USA500 isolates are CP− and provide new insight into the evolution of the USA300 and USA500 lineages.
format	article
author	Susan Boyle-Vavra Xue Li Md Tauqeer Alam Timothy D. Read Julia Sieth Colette Cywes-Bentley Ginette Dobbins Michael Z. David Neha Kumar Samantha J. Eells Loren G. Miller David J. Boxrud Henry F. Chambers Ruth Lynfield Jean C. Lee Robert S. Daum
author_facet	Susan Boyle-Vavra Xue Li Md Tauqeer Alam Timothy D. Read Julia Sieth Colette Cywes-Bentley Ginette Dobbins Michael Z. David Neha Kumar Samantha J. Eells Loren G. Miller David J. Boxrud Henry F. Chambers Ruth Lynfield Jean C. Lee Robert S. Daum
author_sort	Susan Boyle-Vavra
title	USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus
title_short	USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus
title_full	USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus
title_fullStr	USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus
title_full_unstemmed	USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus
title_sort	usa300 and usa500 clonal lineages of <named-content content-type="genus-species">staphylococcus aureus</named-content> do not produce a capsular polysaccharide due to conserved mutations in the <italic toggle="yes">cap5</italic> locus
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/e53591632de24437be907d7162248af0
work_keys_str_mv	AT susanboylevavra usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT xueli usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT mdtauqeeralam usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT timothydread usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT juliasieth usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT colettecywesbentley usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT ginettedobbins usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT michaelzdavid usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT nehakumar usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT samanthajeells usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT lorengmiller usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT davidjboxrud usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT henryfchambers usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT ruthlynfield usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT jeanclee usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus AT robertsdaum usa300andusa500clonallineagesofnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentdonotproduceacapsularpolysaccharideduetoconservedmutationsintheitalictoggleyescap5italiclocus
_version_	1718427677982982144

USA300 and USA500 Clonal Lineages of <named-content content-type="genus-species">Staphylococcus aureus</named-content> Do Not Produce a Capsular Polysaccharide Due to Conserved Mutations in the <italic toggle="yes">cap5</italic> Locus

Ejemplares similares