The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is not required for virulence

Abstract

The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is not required for virulence The Yersinia pseudotuberculosis chromosome contains a seven-gene polycistronic unit (the pmrF operon) whose products share extensive homologies with their pmrF counterparts in Salmonella enterica serovar Typhimurium (S. typhimurium), another Gram-negative bacterial enteropathogen. This gene cluster is essential for addition of 4-aminoarabinose to the lipid moiety of LPS, as demonstrated by MALDI-TOF mass spectrometry of lipid A from both wild-type and pmrF-mutated strains. As in S. typhimurium, 4-aminoarabinose substitution of lipid A contributes to in vitro resistance of Y. pseudotuberculosis to the antimicrobial peptide polymyxin B. Whereas pmrF expression in S. typhimurium is mediated by both the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems, it appears to be PmrA-PmrB-independent in Y. pseudotuberculosis, with the response regulator PhoP interacting directly with the pmrF operon promoter region. This result reveals that the ubiquitous PmrA-PmrB regulatory system controls different regulons in distinct bacterial species. In addition, pmrF inactivation in Y. pseudotuberculosis has no effect on bacterial virulence in the mouse, again in contrast to the situation in S. typhimurium. The marked differences in pmrF operon regulation in these two phylogenetically close bacterial species may be related to their dissimilar lifestyles.

An iron-regulated LysR-type element mediates antimicrobial peptide resistance and virulence in Yersinia pseudotuberculosis

“…We had previously observed that when exponentially growing Y. pseudotuberculosis IP32777 was inoculated into growth medium supplemented with the iron chelators desferral or 2,2-dipyridyl, the resistance of the bacterium to polymyxin B increased about 20-fold (Marceau et al, 2004). In the present study, we assessed whether this phenotype could also be observed in the closely related enteropathogenic species Y. enterocolitica (Bottone, 1997) under iron availability limitation conditions.…”

“…Conversely, expression of this gene was diminished by nearly threefold in Y. pseudotuberculosis after inactivation of YPTB0333. Although this reduction was not statistically significant [most likely because pmrF transcription has been shown to be regulated by other means, such as the two-component system regulator PhoP (Marceau et al, 2004)], YPTB0333…”

“…In a previous study (Marceau et al, 2004), we observed an increase in Y. pseudotuberculosis resistance to polymyxin B (the benchmark cationic antimicrobial peptide) when bacteria were grown under iron-starvation conditions: to the best of our knowledge, such a phenotype had not been reported for any bacteria. We have now identified the genetic determinant of inducible resistance to polymyxin B in Y. pseudotuberculosis and demonstrate that one of the genes involved contributes to bacterial virulence and promotes intestinal colonization by the enteropathogen.…”

Characterization of Xylella fastidiosa popP Gene Required for Pathogenicitya

“…TCS PhoP-PhoQ system of Salmonella and Yersinia pestis is responsible for the virulence within animal host cells [13][14][15]. PhoPPhoQ of X. oryzae pv.…”

“…Salmonella species are facultative intracellular pathogens that can infect a wide variety of animals causing different diseases [12]. A phoP mutant of the etiologic agent of bubonic plagues Yersinia pestis [13,14], reduced the abilities to survival within macrophages, and increased sensitivity to low pH, oxidative stress, and high osmolarity [15]. A phoP deficient of Shigella is hypersensitive to killing by neutrophils [16].…”