AI Article Synopsis

  • MpeR, a transcriptional regulator in Neisseria gonorrhoeae, represses the mtrF gene, which is crucial for the function of the Mtr efflux pump that helps the bacteria resist antimicrobials.
  • The regulation of mpeR is influenced by iron availability, suggesting a link between iron levels and the expression of an interconnected regulatory system that modulates antibiotic resistance.
  • Microarray analysis revealed that under low iron conditions, MpeR directly represses the mtrR gene, leading to increased expression of the mtrCDE efflux pump and enhancing gonococcal resistance to specific antimicrobial agents.

Article Abstract

Previous studies have shown that the MpeR transcriptional regulator produced by Neisseria gonorrhoeae represses the expression of mtrF, which encodes a putative inner membrane protein (MtrF). MtrF works as an accessory protein with the Mtr efflux pump, helping gonococci to resist high levels of diverse hydrophobic antimicrobials. Regulation of mpeR has been reported to occur by an iron-dependent mechanism involving Fur (ferric uptake regulator). Collectively, these observations suggest the presence of an interconnected regulatory system in gonococci that modulates the expression of efflux pump protein-encoding genes in an iron-responsive manner. Herein, we describe this connection and report that levels of gonococcal resistance to a substrate of the mtrCDE-encoded efflux pump can be modulated by MpeR and the availability of free iron. Using microarray analysis, we found that the mtrR gene, which encodes a direct repressor (MtrR) of mtrCDE, is an MpeR-repressed determinant in the late logarithmic phase of growth when free iron levels would be reduced due to bacterial consumption. This repression was enhanced under conditions of iron limitation and resulted in increased expression of the mtrCDE efflux pump operon. Furthermore, as judged by DNA-binding analysis, MpeR-mediated repression of mtrR was direct. Collectively, our results indicate that both genetic and physiologic parameters (e.g., iron availability) can influence the expression of the mtr efflux system and modulate levels of gonococcal susceptibility to efflux pump substrates.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3294918PMC
http://dx.doi.org/10.1128/AAC.06112-11DOI Listing

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