The NH2-Terminal region of streptococcus pyogenes M5 protein confers protection against degradation by proteases and enhances mucosal colonization of mice

Thomas A. Penfound, Itzhak Ofek, Harry S. Courtney, David L. Hasty, James B. Dale

Research output: Contribution to journalArticlepeer-review

Abstract

Background. The NH2-terminal sequence of the M protein from group A streptococci defines the serotype of the organism and contains epitopes that evoke bactericidal antibodies. Methods. To identify additional roles for this region of the M protein, we constructed a mutant of M5 group A streptococci expressing an M protein with a deletion of amino acid residues 3-22 (ΔNH2). Results. M5 streptococci and the ΔNH2 mutant were resistant to phagocytosis and were similarly virulent in mice. However, ΔNH2 was significantly less hydrophobic, contained less lipoteichoic acid on its surface, and demonstrated reduced adherence to epithelial cells. These differences were abolished when organisms were grown in the presence of protease inhibitors. Treatment with cysteine proteases or with human saliva resulted in the release of M protein from the ΔNH2 mutant at a significantly greater rate than observed with the wild-type M5 strain. Compared with the parent strain, the ΔNH2 strain also showed a significant reduction in its ability to colonize the upper respiratory mucosa of mice. Conclusions. The NH2 terminus of M5 protein has an important role in protecting the surface protein from proteolytic cleavage, thus preserving its function as an anchor for lipoteichoic acid, which is a primary mediator of adherence to epithelial cells and colonization.

Original languageEnglish
Pages (from-to)1580-1588
Number of pages9
JournalJournal of Infectious Diseases
Volume201
Issue number10
DOIs
StatePublished - 15 May 2010

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