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PMID:18978065

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Citation

Folster, JP, Johnson, PJ, Jackson, L, Dhulipali, V, Dyer, DW and Shafer, WM (2009) MtrR modulates rpoH expression and levels of antimicrobial resistance in Neisseria gonorrhoeae. J. Bacteriol. 191:287-97

Abstract

The MtrR transcriptional-regulatory protein is known to repress transcription of the mtrCDE operon, which encodes a multidrug efflux pump possessed by Neisseria gonorrhoeae that is important in the ability of gonococci to resist certain hydrophobic antibiotics, detergents, dyes, and host-derived antimicrobials. In order to determine whether MtrR can exert regulatory action on other gonococcal genes, we performed a whole-genome microarray analysis using total RNA extracted from actively growing broth cultures of isogenic MtrR-positive and MtrR-negative gonococci. We determined that, at a minimum, 69 genes are directly or indirectly subject to MtrR control, with 47 being MtrR repressed and 22 being MtrR activated. rpoH, which encodes the general stress response sigma factor RpoH (sigma 32), was found by DNA-binding studies to be directly repressed by MtrR, as it was found to bind to a DNA sequence upstream of rpoH that included sites within the rpoH promoter. MtrR also repressed the expression of certain RpoH-regulated genes, but this regulation was likely indirect and a reflection of MtrR control of rpoH expression. Inducible expression of MtrR was found to repress rpoH expression and to increase gonococcal susceptibility to hydrogen peroxide (H(2)O(2)) and an antibiotic (erythromycin) recognized by the MtrC-MtrD-MtrE efflux pump system. We propose that, apart from its ability to control the expression of the mtrCDE-encoded efflux pump operon and, as a consequence, levels of gonococcal resistance to host antimicrobials (e.g., antimicrobial peptides) recognized by the efflux pump, the ability of MtrR to regulate the expression levels of rpoH and RpoH-regulated genes also modulates levels of gonococcal susceptibility to H(2)O(2).

Links

PubMed PMC2612434 Online version:10.1128/JB.01165-08

Keywords

Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Chromosome Mapping; Chromosomes, Bacterial/genetics; DNA Primers; DNA, Bacterial/genetics; DNA, Complementary/genetics; Deoxyribonuclease I; Drug Resistance, Microbial/genetics; Gene Expression Regulation, Bacterial; Genotype; Heat-Shock Proteins/genetics; Humans; Hydrogen Peroxide/pharmacology; Neisseria gonorrhoeae/genetics; Nucleic Acid Hybridization; Operon; Polymerase Chain Reaction; Repressor Proteins/genetics; Repressor Proteins/metabolism; Sigma Factor/genetics; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

NEIGO:MTRR

GO:0016566: specific transcriptional repressor activity

ECO:0000270:

F

Figure 3 illustrates down regulation of rpoH in several strains.

complete


See also

References

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