Transcriptional profiling of the mutant in reveals regulatory connection with the operon Free

Abstract

ClpX functions as either an independent chaperone or a component of the ClpXP protease, a conserved intracellular protease that acts as a global regulator in the bacterial cell by degrading regulatory proteins, stress response proteins and rate-limiting enzymes. Previously, we found that loss of in Sterne leads to increased susceptibility to antimicrobial agents that target the cell envelope. The aim of this study was to identify genes within the regulatory network of that contribute to antimicrobial resistance. Using microarray analysis, we found 119 genes that are highly differentially expressed in the ∆ mutant, with the majority involved in metabolic, transport or regulatory functions. Several of these differentially expressed genes, including , , , and , are associated with cell wall-active antibiotics in other bacterial species. We focused on and , which form the operon and are downregulated in ∆, because loss of increases autolytic activity and penicillin susceptibility in . While we observed no changes in autolytic activity in either ∆ or ∆ Sterne, we find that both mutants have increased susceptibility to the antimicrobial peptide LL-37 and daptomycin. However, phenotypes between ∆ and ∆ are not identical as ∆ also displays increased susceptibility to penicillin and nisin but ∆ does not. Therefore, while decreased expression of may be partially responsible for the increased antimicrobial susceptibility seen in the ∆ mutant, disruption of other pathways must also contribute to this phenotype.

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2018-04-01
2024-03-28
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