Unknown,Transcriptomics,Genomics,Proteomics

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MpeR regulation in Neisseria gonorrhoeae (F19) through an iron-responsive mechanism


ABSTRACT: Previous studies have shown that the MpeR transcriptional regulator produced by Neisseria gonorrhoeae represses expression of mtrF, which encodes a putative inner membrane protein that works with the MtrC-MtrD-MtrE efflux pump to allow gonococci to resist high levels of multiple 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 expression of drug 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 the direct transcriptional 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. MpeR-mediated repression of mtrR appeared to be direct, as judged by DNA-binding analyses, and was enhanced by conditions of iron-limitation, which resulted in increased expression of the mtrCDE efflux pump operon. Taken together, our results indicate that both genetic and physiologic parameters can influence expression of the mtr efflux system and that these can modulate levels of gonococcal susceptibility to efflux pump substrates. two strains, two growth phases, three replicates each.

ORGANISM(S): Neisseria gonorrhoeae

SUBMITTER: Lydgia Jackson 

PROVIDER: E-GEOD-32717 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MpeR regulates the mtr efflux locus in Neisseria gonorrhoeae and modulates antimicrobial resistance by an iron-responsive mechanism.

Mercante Alexandra Dubon AD   Jackson Lydgia L   Johnson Paul J T PJ   Stringer Virginia A VA   Dyer David W DW   Shafer William M WM  

Antimicrobial agents and chemotherapy 20120103 3


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 prese  ...[more]

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