4.7 Article

Role of AxyABM overexpression in acquired resistance in Achromobacter xylosoxidans

期刊

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 77, 期 4, 页码 926-929

出版社

OXFORD UNIV PRESS
DOI: 10.1093/jac/dkab479

关键词

-

资金

  1. Biology and Pathology Centre of the University Hospital of Dijon

向作者/读者索取更多资源

The AxyABM efflux system plays a significant role in the acquired resistance of Achromobacter to commonly used antibiotics in CF patients, including ciprofloxacin, meropenem, and ceftazidime. Overproduction of AxyABM may also lead to increased minimum inhibitory concentration of the new promising antibiotic cefiderocol.
Background Acquired antimicrobial resistance among Achromobacter isolates from cystic fibrosis (CF) patients is frequent. Data concerning the mechanisms involved are scarce. The role of the AxyXY-OprZ and AxyEF-OprN Resistance Nodulation Division (RND) efflux systems has been demonstrated, but not that of AxyABM. Objectives To explore the role of efflux systems in the acquired multiresistance observed in a one-step mutant selected after ofloxacin exposure. Methods The in vitro resistant mutant NCF-39-Bo2 and its parental strain NCF-39 (MICs of meropenem of 8 and 0.19 mg/L, of ceftazidime of 12 and 3 mg/L, of cefiderocol of 0.094 and 0.032 mg/L and of ciprofloxacin of 8 and 1.5 mg/L, respectively) were investigated by RNA-seq and WGS. Gene inactivation and reverse transcription quantitative PCR (RT-qPCR) were used to explore the role of the efflux systems of interest. Results RNA-seq showed that the AxyABM efflux system was overproduced (about 40-fold) in the in vitro mutant NCF-39-Bo2 versus its parental strain NCF-39. A substitution in AxyR, the putative regulator of AxyABM, was detected in NCF-39-Bo2. Gene inactivation of axyB (encoding the transporter component) in NCF-39-Bo2 led to a decrease in MICs of ciprofloxacin (5-fold), meropenem (64-fold), ceftazidime (12-fold) and cefiderocol (24-fold). Inactivation of axyB in the clinical isolate AXX-H2 harbouring a phenotype of resistance close to that of NCF-39-Bo2 enhanced the activity of the same molecules, especially meropenem. Conclusions AxyABM overproduction is involved in acquired resistance of Achromobacter to ciprofloxacin, meropenem and ceftazidime, antibiotics widely used in CF patients, and increases the MIC of the new promising antibiotic cefiderocol.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据