M protein and hyaluronic acid capsule are essential for in vivo selection of covRS mutations characteristic of invasive serotype M1T1 group A Streptococcus

Cole, JN, Pence, MA, von Kockritz-Blickwede, M, Hollands, A, Gallo, RL, Walker, MJ and Nizet, V (2010) M protein and hyaluronic acid capsule are essential for in vivo selection of covRS mutations characteristic of invasive serotype M1T1 group A Streptococcus. mBio, 1 4: e00191-10-1-e00191-10-8. doi:10.1128/mBio.00191-10


Author Cole, JN
Pence, MA
von Kockritz-Blickwede, M
Hollands, A
Gallo, RL
Walker, MJ
Nizet, V
Title M protein and hyaluronic acid capsule are essential for in vivo selection of covRS mutations characteristic of invasive serotype M1T1 group A Streptococcus
Journal name mBio   Check publisher's open access policy
ISSN 2150-7511
Publication date 2010-08-31
Sub-type Article (original research)
DOI 10.1128/mBio.00191-10
Open Access Status DOI
Volume 1
Issue 4
Start page e00191-10-1
End page e00191-10-8
Total pages 8
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2011
Language eng
Formatted abstract
The initiation of hyperinvasive disease in group A Streptococcus (GAS) serotype M1T1 occurs by mutation within the covRS two-component regulon (named covRS for control of virulence regulatory sensor kinase), which promotes resistance to neutrophil-mediated killing through the upregulation of bacteriophage-encoded Sda1 DNase. To determine whether other virulence factors contribute to this phase-switching phenomenon, we studied a panel of 10 isogenic GAS serotype M1T1 virulence gene knockout mutants. While loss of several individual virulence factors did not prevent GAS covRS switching in vivo, we found that M1 protein and hyaluronic acid capsule are indispensable for the switching phenotype, a phenomenon previously attributed uniquely to the Sda1 DNase. We demonstrate that like M1 protein and Sda1, capsule expression enhances survival of GAS serotype M1T1 within neutrophil extracellular traps. Furthermore, capsule shares with M1 protein a role in GAS resistance to human cathelicidin antimicrobial peptide LL-37. We conclude that a quorum of GAS serotype M1T1 virulence genes with cooperative roles in resistance to neutrophil extracellular killing is essential for the switch to a hyperinvasive phenotype in vivo.

Importance
The pathogen group A Streptococcus (GAS) causes a wide range of human infections ranging from the superficial “strep throat” to potentially life-threatening conditions, such as necrotizing fasciitis, also known as “flesh-eating disease.” A marked increase in the number of cases of severe invasive GAS infection during the last 30 years has been traced to the emergence and spread of a single clone of the M1T1 serotype. Recent studies have shown that GAS serotype M1T1 bacteria undergo a genetic “switch” in vivo to a hypervirulent state that allows dissemination into the bloodstream. The present study was undertaken to identify specific GAS serotype M1T1 virulence factors required for this switch to hypervirulence. The surface-anchored GAS M1 protein and hyaluronic acid capsule are found to be essential for the switching phenotype, and a novel role for capsule in GAS resistance to host defense peptides and neutrophil extracellular killing is revealed.
Copyright © 2010 Cole et al.
Keyword Neutrophil extraceullar traps
Streptolysin-S
Antimicrobial peptides
Cycteine protease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e00191-10. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sun, 26 Dec 2010, 10:03:33 EST