1887

Abstract

possesses a lone xtraytoplasmic unction (ECF) sigma factor, σ. In , the ECF sigma factor, σ, is activated through a proteolytic cascade that begins with cleavage of the RsiW anti-sigma factor by a site-1 protease (S1P), PrsW. We have identified a PrsW homologue in (termed PrsS) and explored its role in σ regulation. Herein, we demonstrate that although a cognate σ anti-sigma factor currently remains elusive, phenocopies in a wealth of regards. Specifically, expression mimics the upregulation observed for in response to DNA-damaging agents, cell wall-targeting antibiotics and during growth in human serum and murine macrophages. mutants also display the same sensitivities of mutants to the DNA-damaging agents methyl methane sulfonate (MMS) and hydrogen peroxide, and the cell wall-targeting antibiotics ampicillin, bacitracin and penicillin-G. These phenotypes appear to be explained by alterations in abundance of proteins involved in drug resistance (Pbp2a, FemB, HmrA) and the response to DNA damage (BmrA, Hpt, Tag). Our findings seem to be mediated by putative proteolytic activity of PrsS, as site-directed mutagenesis of predicted catalytic residues fails to rescue the sensitivity of the mutant to HO and MMS. Finally, a role for PrsS in virulence was identified using human and murine models of infection. Collectively, our data indicate that PrsS and σ function in a similar manner, and perhaps mediate virulence and resistance to DNA damage and cell wall-targeting antibiotics, via a common pathway.

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2015-05-01
2019-10-21
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