A naturally occurring single amino acid replacement in multiple gene regulator of group a streptococcus significantly increases virulence

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dc.creatorMisu Sanson
dc.date2014
dc.date.accessioned2018-10-19T13:37:35Z
dc.date.available2018-10-19T13:37:35Z
dc.descriptionSingle-nucleotide polymorphisms (SNPs) are the most common source of genetic variation within a species; however, few investigations demonstrate how naturally occurring SNPs may increase strain virulence. We recently used group A Streptococcus as a model pathogen to study bacteria strain genotype-patient disease phenotype relationships. Whole-genome sequencing of approximately 800 serotype M59 group A Streptococcus strains, recovered during an outbreak of severe invasive infections across North America, identified a disproportionate number of SNPs in the gene encoding multiple gene regulator of group A Streptococcus (mga). Herein, we report results of studies designed to test the hypothesis that the most commonly occurring SNP, encoding a replacement of arginine for histidine at codon 201 of Mga (H201R), significantly increases virulence. Whole transcriptome analysis revealed that the H201R replacement significantly increased expression of mga and 54 other genes, including many proven virulence factors. Compared to the wild-type strain, a H201R isogenic mutant strain caused significantly larger skin lesions in mice. Serial quantitative bacterial culture and noninvasive magnetic resonance imaging also demonstrated that the isogenic H201R strain was significantly more virulent in a nonhuman primate model of joint infection. These findings show that the H201R replacement in Mga increases the virulence of M59 group A Streptococcus and provide new insight to how a naturally occurring SNP in bacteria contributes to human disease phenotypes. Copyright © 2015 American Society for Investigative Pathology.
dc.identifier.doi10.1016/j.ajpath.2014.10.018
dc.identifier.endpage471
dc.identifier.issn29440
dc.identifier.issue2
dc.identifier.startpage462
dc.identifier.urihttp://hdl.handle.net/11285/630618
dc.identifier.volume185
dc.languageeng
dc.publisherElsevier Inc.
dc.relationhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84922329254&doi=10.1016%2fj.ajpath.2014.10.018&partnerID=40&md5=af7cf4e7850033519e64fcb26f51e313
dc.relationInvestigadores
dc.relationEstudiantes
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0
dc.sourceAmerican Journal of Pathology
dc.subjectamino acid
dc.subjectarginine
dc.subjectbacterial protein
dc.subjecthistidine
dc.subjectprotein Mga
dc.subjecttranscriptome
dc.subjectunclassified drug
dc.subjectvirulence factor
dc.subjectbacterial protein
dc.subjectmry protein, Streptococcus pyogenes
dc.subjectamino acid substitution
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectArticle
dc.subjectbacterial gene
dc.subjectbacterial genome
dc.subjectbacterial strain
dc.subjectbacterial virulence
dc.subjectbacterium culture
dc.subjectcodon
dc.subjectcontrolled study
dc.subjectgene expression
dc.subjectgene sequence
dc.subjecthuman
dc.subjecthuman cell
dc.subjectinfectious arthritis
dc.subjectMacaca fascicularis
dc.subjectmga gene
dc.subjectmouse
dc.subjectnonhuman
dc.subjectnuclear magnetic resonance imaging
dc.subjectphenotype
dc.subjectpriority journal
dc.subjectregulator gene
dc.subjectsingle nucleotide polymorphism
dc.subjectskin infection
dc.subjectsoft tissue infection
dc.subjectStreptococcus group A
dc.subjectamino acid substitution
dc.subjectanimal
dc.subjectarthropathy
dc.subjectcell line
dc.subjectfemale
dc.subjectgenetics
dc.subjecthairless mouse
dc.subjectmetabolism
dc.subjectmicrobiology
dc.subjectmissense mutation
dc.subjectpathogenicity
dc.subjectpathology
dc.subjectsingle nucleotide polymorphism
dc.subjectStreptococcus infection
dc.subjectStreptococcus pyogenes
dc.subjectAmino Acid Substitution
dc.subjectAnimals
dc.subjectBacterial Proteins
dc.subjectCell Line
dc.subjectFemale
dc.subjectGenome, Bacterial
dc.subjectHumans
dc.subjectJoint Diseases
dc.subjectMice
dc.subjectMice, Hairless
dc.subjectMutation, Missense
dc.subjectPolymorphism, Single Nucleotide
dc.subjectStreptococcal Infections
dc.subjectStreptococcus pyogenes
dc.subject.classification7 INGENIERÍA Y TECNOLOGÍA
dc.titleA naturally occurring single amino acid replacement in multiple gene regulator of group a streptococcus significantly increases virulence
dc.typeArtículo
refterms.dateFOA2018-10-19T13:37:35Z

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