Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of emm89 Streptococcus pyogenes

MBio
Luchang ZhuJames M Musser

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 mec...Continue Reading

References

Mar 24, 2016·Open Forum Infectious Diseases·Jessica Galloway-PeñaVance G Fowler
Jan 31, 2019·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Tadao HasegawaIchiro Tatsuno
Aug 15, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Roberta CretiMonica Imperi
Oct 26, 2018·Frontiers in Microbiology·Catarina PatoPortuguese Group for the Study of Streptococcal Infections
Oct 7, 2016·The Journal of Infectious Diseases·Francesca LatronicoJaana Vuopio
Jan 27, 2017·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·F TaginiG Greub
Aug 8, 2018·Journal of the Pediatric Infectious Diseases Society·Anthony R FloresSamuel A Shelburne
Feb 26, 2019·Case Reports in Infectious Diseases·Morouge AlramadhanAnthony R Flores
Nov 4, 2017·Journal of Medical Microbiology·Stephen B BeresJames M Musser
Nov 15, 2018·Frontiers in Microbiology·Chuan Chiang-NiCheng-Hsun Chiu

Citations

Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·Michael R WesselsT J DiCesare
Jul 25, 2000·Clinical Microbiology Reviews·M W Cunningham
Jan 4, 2005·Biochimica Et Biophysica Acta·Hisashi KimotoAkira Taketo
Dec 8, 2005·PLoS Pathogens·Michael A MeehlMichael G Caparon
Dec 29, 2005·The Journal of Biological Chemistry·Hisashi KimotoAkira Taketo
Jul 20, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jessica DarenbergBirgitta Henriques Normark
Sep 7, 2007·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rosalyn E O'LoughlinActive Bacterial Core Surveillance Team
Jan 23, 2009·Journal of Clinical Microbiology·Bogdan Luca-HarariAftab Jasir
Sep 26, 2009·The Lancet Infectious Diseases·Andrew C SteerJonathan R Carapetis
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Randall J OlsenJames M Musser
Feb 12, 2010·FEMS Immunology and Medical Microbiology·Matthias ImöhlMark van der Linden
Apr 15, 2011·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·M MontesEmilio Pérez-Trallero
Jul 14, 2011·Emerging Infectious Diseases·Atheer SafarLesley Voss
Sep 3, 2011·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·C PlainvertCNR-Strep network
Oct 7, 2011·Journal of Clinical Microbiology·A LepoutreMicrobiologists of the Epibac Network
Nov 22, 2011·Emerging Infectious Diseases·Patrick R SheaJames M Musser
Aug 13, 2013·International Journal of Medical Microbiology : IJMM·Ana FriãesPortuguese Group for the Study of Streptococcal Infections
Sep 4, 2013·The Journal of Infection·Esther TamayoEmilio Pérez-Trallero
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Waleed NasserJames M Musser
Jul 2, 2014·Journal of Medical Microbiology·Nathalie M KarakySima T Tokajian
Feb 24, 2015·Epidemiology and Infection·T IkebeWorking Group for Beta-haemolytic Streptococci in Japan
Aug 11, 2015·The Journal of Clinical Investigation·Luchang ZhuJames M Musser

Related Concepts

Pathologic Cytolysis
Pathogenic Aspects
streptolysin O antigen
KCNMA1
Bacterial Proteins
Pathogenesis
Pathogenicity
Genome
Genes
Microbial Anatomical Capsule Structure

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