Premium
A Naturally Occurring Single Nucleotide Mutation Significantly Impairs Necrotizing Fasciitis (“Flesh Eating”) Capacity of Group A Streptococcus (GAS)
Author(s) -
Olsen Randall J,
Sitkiewicz Izabela,
Ayeras Ara,
Tart Anne,
Lei Benfang,
Blasdel Terry,
Humbird Tammy,
Beres Stephen,
Green Nicole,
Cagle Philip,
Montgomery Charles,
Whitney Adeline,
DeLeo Frank,
Musser James M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.594
Subject(s) - biology , virulence , mutant , streptococcus suis , wild type , streptococcus , complementation , phenotype , microbiology and biotechnology , mutation , gene , genetics , pathogenesis , single nucleotide polymorphism , population , bacteria , genotype , immunology , medicine , environmental health
The relationship between specific single nucleotide mutations and biologically relevant traits among pathogenic bacteria is poorly understood. We recently discovered that a naturally occurring single nucleotide mutation in the group A streptococcus (GAS) metal transporter of streptococcus regulator ( mtsR ) gene was epidemiologically associated with decreased human necrotizing fasciitis (NF). We hypothesized that wild‐type MtsR function is required for GAS to cause the NF phenotype. To test this hypothesis, MtsR wild‐type, isogenic mutant, and complemented variants of strain MGAS315 were compared in mouse and nonhuman primate models of NF. Virulence studies included microscopic examination, quantitative cultures, phagocytosis assays and expression microarray analysis. Compared to the parental strain, the mtsR mutant strain was significantly less able to cause NF in mice and macaques. Importantly, mtsR mutation resulted in reduced tissue necrosis and vascular dissemination. Gene complementation restored the wild‐type virulence characteristics. In conclusion, a naturally‐occurring single nucleotide mutation dramatically altered the virulence characteristics of GAS in NF. This finding has broad implications for the confluence of population genomics, bacterial pathogenesis and translational research.