Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae
| Autor: | Douglas M. Warner, William M. Shafer, Ann E. Jerse, Jason P. Folster |
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| Rok vydání: | 2008 |
| Předmět: |
Operon
Lipoproteins Mutant Biology medicine.disease_cause Bacterial genetics Microbiology Gonorrhea Mice Bacterial Proteins Drug Resistance Multiple Bacterial medicine Immunology and Allergy Animals Derepression Genetics Mice Inbred BALB C Activator (genetics) Membrane Proteins Membrane Transport Proteins Gene Expression Regulation Bacterial MTRR Neisseria gonorrhoeae Repressor Proteins Infectious Diseases Mutation Female Efflux Bacterial Outer Membrane Proteins |
| Zdroj: | The Journal of infectious diseases. 196(12) |
| ISSN: | 0022-1899 |
| Popis: | The Neisseria gonorrhoeae MtrC-MtrD-MtrE multidrug-resistance efflux pump expels macrolide antibiotics, penicillin, and antimicrobial effectors of the innate defense. Mutation of the mtrR locus, which encodes a transcriptional repressor of the mtrCDE operon, increases gonococcal resistance to these agents. Here we report that, in a mouse infection model, an mtrR mutant is more fit than the wild-type bacteria. Consistent with derepression of the mtrCDE operon as the primary reason for the fitness benefit, an mtrR,mtrE double mutant and an mtrE mutant showed no difference in survival phenotype. Gonococcal mutants deficient in MtrA, an activator of the mtrCDE operon, exhibited significantly reduced fitness in vivo, and mtrA mutants with spontaneous compensatory mtrR mutations were selected during infection. These results confirm the importance of the MtrC-MtrD-MtrE efflux-pump system during experimental gonococcal genital-tract infection and also illustrate an antibiotic-resistance mechanism that is accompanied by a fitness benefit rather than a fitness cost. |
| Databáze: | OpenAIRE |
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