Outer membrane proteins responsible for multiple-drug resistance in proteus vulgaris

ABSTRACT

The role of outer membrane proteins in the development of multiple-drug resistance in Proteus vulgaris. Three Proteus vulgaris clinical isolates obtained from Microbiology laporatory at King Abdul Aziz University Hospitals. One of these isolates that is characterized by its sensitivity to all the used antimicrobial agents was selected for further studies. A total of 5 spontaneous ciprofloxacin-resistant mutants were isolated from Proteus vulgaris clinical isolate on agar plates containing ciprofloxacin at concentration of 6 MIC. Four of these mutants [PvM2-PvM5] are characterized by cross-resistance to other fluoroquinolones [norfloxacin. and ofloxacin], beta-lactam antibiotics [cefamandole, cefoperazone, cefotaxime, ceftazidime, ceftriaxone, and cefepime], and aztreonam. While the fifth mutant [PvM1] is characterized by selective resistance to the tested fluoroquinolones. The outer membrane proteins [OMPs] analysis showed a significant reduction [in PvM4 and PvM5 mutants] or disappearance [in PvM2 and PvM3 mutants] of 39 KDa OMP as compared to the parent isolate. In case of mutant PvM1, no significant change in the OMP profile was observed. The four multiple-drug resistant mutants [PvM2-PvM5] had about 2.3 to 3.8 time lower rate of norfloxacin uptake than that of the parent isolate, while no significant change in norfloxain uptake was observed in case of PvM1 mutant. The results of beta-lactamase induction and DNA gyrase assay showed no difference between the selected mutants and their parent, with exception for PvM1 mutant in a which a significant decrease in the DNA gyrase sensitivity to ciprofloxacin was observed. Reduction or disappearance of 39 KDa OMPs in P. vulgaris isolate is associated with cross-resistance to fluoroquinolones. Beta-Iactam antibiotics, and aztreonam