Shigemura Katsumi, Osawa Kayo, Kato Ayaka, Tokimatsu Issei, Arakawa Soichi, Shirakawa Toshiro, Fujisawa Masato
Division of Urology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Infection Control and Prevention, Kobe University Hospital, Kobe, Japan.
J Antibiot (Tokyo). 2015 Sep;68(9):568-72. doi: 10.1038/ja.2015.34. Epub 2015 Apr 8.
There are several mechanisms for antibiotic-resistant Pseudomonas aeruginosa. The purpose of this study is to investigate the association between the expression of efflux pump-coding genes and antibiotic resistance in P. aeruginosa causing urinary tract infections (UTIs). We extracted the RNA from 105 clinical strains of P. aeruginosa isolated from UTI patients with full data on antibiotic MICs and assayed real-time quantitative reverse-transcription PCR. We investigated the gene expressions of four resistance nodulation cell division-type multi-drug efflux pump systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY(-OprA)) and the correlation of the MICs of nine antibiotics, risk factors and antibiotic resistance-related genes with expressions of mexB, mexC, mexE and mexY. Multivariate statistical data demonstrated a significant relationship between increased expression of mexB or mexC and complicated UTI (Odds ratio=8.03, P<0.001 and Odds ratio=8.86, P=0.032, respectively). We also found a significant association between the increased expression of mexC and resistance to levofloxacin (LVFX) (Odds ratio=4.48, P=0.035). In conclusion, increased expression of mexC leads to LVFX resistance in P. aeruginosa causing UTI. These results contribute to our knowledge of the efflux pump system and antibiotic resistance.
铜绿假单胞菌产生抗生素耐药性有多种机制。本研究的目的是调查导致尿路感染(UTIs)的铜绿假单胞菌中流出泵编码基因的表达与抗生素耐药性之间的关联。我们从105株从UTI患者中分离出的铜绿假单胞菌临床菌株中提取RNA,这些菌株有完整的抗生素MIC数据,并进行实时定量逆转录PCR检测。我们研究了四种耐药结节化细胞分裂型多药流出泵系统(MexAB-OprM、MexCD-OprJ、MexEF-OprN和MexXY(-OprA))的基因表达,以及九种抗生素的MIC、危险因素和抗生素耐药相关基因与mexB、mexC、mexE和mexY表达之间的相关性。多变量统计数据表明,mexB或mexC表达增加与复杂性UTI之间存在显著关系(优势比分别为8.03,P<0.001和8.86,P=0.032)。我们还发现mexC表达增加与对左氧氟沙星(LVFX)耐药之间存在显著关联(优势比=4.48,P=0.035)。总之,mexC表达增加会导致引起UTI的铜绿假单胞菌对LVFX产生耐药性。这些结果有助于我们了解流出泵系统和抗生素耐药性。