Deletion of atoR from Streptococcus pyogenes Results in Hypervirulence in a Mouse Model of Sepsis and is LuxS Independent

Group A Streptococcus (GAS) is a Gram-positive human pathogen that causes a variety of diseases ranging from pharyngitis to life-threaten­ing streptococcal toxic shock syndrome. Recently, several global gene expression analyses have yielded extensive new information regarding the regulation of genes encoding known and putative virulence factors in GAS. A microarray analysis found that transcription of the GAS gene M5005_Spy_1343 was significantly increased in response to interaction with human polymorphonuclear leukocytes. M5005_Spy_1343 is predicted to encode a member of the LysR family of transcriptional regulators and is located upstream of a putative operon containing six genes. Five of these genes have sequence similarity to genes involved in short-chain fatty acid metabolism, whereas the sixth gene (luxS) is found in many bacterial species and is involved in quorum sensing. Unexpectedly, inactivation of the M5005_Spy_1343 gene resultedin hypervirulence in an intraperitoneal mouse model of infection. Increased virulence was not due to changes in luxS gene expression.We postulate that short-chain fatty acid metabolism is involved in GAS pathogenesis