1887

Abstract

is the leading cause of bacterial sepsis and meningitis in neonates and is also the causative agent of several serious infections in immunocompromised adults. encounters multiple niches during an infection, suggesting that regulatory mechanisms control the expression of specific virulence factors in this bacterium. The present study describes the functional characterization of a gene from , designated , which encodes a protein with significant similarity to members of the RofA-like protein (RALP) family of transcriptional regulators. After deletion of the gene in the genome of , the mutant strain exhibited significantly reduced expression of the genes and which encode a serine-rich repeat surface glycoprotein and a pilus protein, respectively, and moderately increased expression of the gene, which encodes a fibrinogen-binding protein. Electrophoretic mobility shift assays demonstrated specific DNA binding of purified Rga to the promoter regions of and , suggesting that Rga directly controls and . Adherence assays revealed significantly reduced binding of the Δ mutant to epithelial HEp-2 cells and to immobilized human keratin 4, respectively. In contrast, the adherence of the Δ mutant to A549 cells and its binding to human fibrinogen was significantly increased. Immunoblot and immunoelectron microscopy revealed that the quantity of pilus structures was significantly reduced in the Δ mutant compared with the parental strain. The wild-type phenotype could be restored by plasmid-mediated expression of , demonstrating that the mutant phenotypes resulted from a loss of Rga function.

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2011-08-01
2019-11-21
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