TheluxSGene ofStreptococcus pyogenesRegulates Expression of Genes That Affect Internalization by Epithelial Cells

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Abstract
The gram-positive pathogenStreptococcus pyogeneswas recently reported to possess a homologue of theluxSgene that is responsible for the production of autoinducer 2, which participates in quorum sensing of both gram-positive and gram-negative bacteria. To test the effect of LuxS on streptococcal internalization, a LuxS mutant was constructed in strain SP268, an invasive M3 serotype. Functional analysis of the mutant revealed that it was internalized by HEp-2 cells with higher efficiency than the wild type (wt). Several genes, includinghasA(hyaluronic acid synthesis),speB(streptococcal pyrogenic exotoxin B), andcsrR(capsule synthesis regulator), a part of a two-component regulatory system, are known to affect the internalization of strain SP268 (J. Jadoun, O. Eyal, and S. Sela, Infect. Immun.70:462-469, 2002). Therefore, the expression of these genes in the mutant and in the wt was examined. LuxS mutation significantly reduced the mRNA level ofspeBand increased the mRNA level ofemm3. No substantial effect was observed on transcription ofhasAandcsrR. Yet less hyaluronic acid capsule was expressed in the mutant. Further analysis revealed thatluxSis under the regulation of the two-component global regulator CsrR. Our results indicate that LuxS activity in strain SP268 plays an important role in the expression of virulence factors associated with epithelial cell internalization.

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