Abstract
We investigated the relationship between the outer membrane protein OprD2 and carbapenem-resistance in 141 clinical isolates of Pseudomonas aeruginosa collected between January and December 2013 from the First Affiliated Hospital of Anhui Medical University in China. Agar dilution methods were employed to determine the minimum inhibitory concentration of meropenem (MEM) and imipenem (IMP) for P. aeruginosa. The gene encoding OprD2 was amplified from141 P. aeruginosa isolates and analyzed by PCR and DNA sequencing. Differences between the effects of IMPR and IMPS groups on the resistance of the P. aeruginosa were observed by SDS-poly acrylamide gel electrophoresis (SDS-PAGE). Three resistance types were classified in the 141 carbapenem-resistant P. aeruginosa (CRPA) isolates tested, namely IMPRMEMR (66.7%), IMPRMEMS (32.6%), and IMPRMEMS (0.7%). DNA sequencing revealed significant diverse gene mutations in the OprD2-encoding gene in these strains. Thirty-four strains had large fragment deletions in the OprD2gene, in 6 strains the gene contained fragment inserts, and in 96 resistant strains, the gene featured small fragment deletions or multi-site mutations. Only 4 metallo-β-lactamase strains and 1 imipenem-sensitive (meropenem-resistant) strain showed a normal OprD2 gene. Using SDS-PAGE to detect the outer membrane protein in 16 CRPA isolates, it was found that 10 IMPRMEMR strains and 5 IMPRMEMS strains had lost the OprD2 protein, while the IMPSMEMR strain contained a normal 46-kDa protein. In conclusion, mutation or loss of the OprD2-encoding gene caused the loss of OprD2, which further led to carbapenem-resistance of P. aeruginosa. Our findings provide insights into the mechanism of carbapenem resistance in P. aeruginosa.
Highlights
Pseudomonas aeruginosa was ranked first among all antibiotic-resistant gram-negative strains according to the China National Antimicrobial Resistance Investigation Net annual report of PLOS ONE | DOI:10.1371/journal.pone.0139995 October 6, 2015Role of OprD2 in Carbapenem Resistance2011[1]
Three types of strains were categorized according to their resistance to imipenem and meropenem: IMPRMEMR (94/141) was predominant and accounted for 66.7%, IMPRMEMS accounted for 32.6% (46/141), and only a single IMPSMEMR strain was detected and accounted for only 0.7% (1/141)
The increasing prevalence of health care-associated infections caused by multidrug resistant P. aeruginosa (MDR-PA) is severely compromising the selection of appropriate treatments and is associated with high morbidity and mortality[13]
Summary
Pseudomonas aeruginosa was ranked first among all antibiotic-resistant gram-negative strains according to the China National Antimicrobial Resistance Investigation Net annual report of PLOS ONE | DOI:10.1371/journal.pone.0139995 October 6, 2015Role of OprD2 in Carbapenem Resistance2011[1]. Pseudomonas aeruginosa was ranked first among all antibiotic-resistant gram-negative strains according to the China National Antimicrobial Resistance Investigation Net annual report of PLOS ONE | DOI:10.1371/journal.pone.0139995. It was listed as one of the main pathogenic bacteria in nosocomial infection owing to its capacity to develop resistance to multiple classes of antimicrobials through intrinsic mechanisms and through the acquisition of transferable resistance determinants [2]. In spite of its resistance, P. aeruginosa continued to remain sensitive to carbapenems; imipenemis one of the most frequently used drugs for the treatment of P. aeruginosa infections in China. The accumulation of carbapenem-resistant mechanisms could probably further increase carbapenem MICs, leaving even fewer therapy options for clinicians against the multi-drug resistant P. aeruginosa [3]. P. aeruginosa infections are difficult to cure and have become life threatening
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