Characterization of TolC efflux pump proteins from Pasteurella multocida
Tamas Hatfaludi1, Keith Al-Hasani, Michelle Dunstone
1Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, VIC 3800, Australia.
Antimicrobial Agents and Chemotherapy
|August 30, 2008
Summary
Two Pasteurella multocida TolC homologs, PM0527 and PM1980, were identified. Mutants lacking these proteins showed increased susceptibility to various antibiotics and chemicals, highlighting their role in drug resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Pathogenesis
Background:
- Pasteurella multocida is a significant bacterial pathogen.
- TolC proteins are essential components of tripartite efflux pumps in Gram-negative bacteria.
- Efflux pumps contribute to antimicrobial resistance.
Purpose of the Study:
- To identify and characterize TolC homologs in Pasteurella multocida.
- To investigate the role of these homologs in the susceptibility of P. multocida to antimicrobial agents and chemicals.
Main Methods:
- Bioinformatic identification of TolC homologs (PM0527 and PM1980) in Pasteurella multocida.
- Construction and phenotypic analysis of individual gene deletion mutants (pm0527 and pm1980).
- Determination of minimal inhibitory concentrations (MICs) for various antibiotics and chemicals against wild-type and mutant strains.
Main Results:
- Two TolC homologs, PM0527 and PM1980, were identified in Pasteurella multocida.
- The pm0527 mutant exhibited significantly increased susceptibility to rifampin (512-fold) and acridine orange (128-fold).
- The pm1980 mutant displayed heightened susceptibility to rifampin, ceftazidime, and vancomycin.
Conclusions:
- PM0527 and PM1980 are functional TolC homologs in Pasteurella multocida.
- These proteins play a role in the multidrug efflux system of P. multocida.
- Targeting these TolC homologs could be a potential strategy to enhance the efficacy of existing antibiotics against P. multocida infections.
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