한빛사논문
Do‑Hoon Lee1†, Ju‑Hee Cha1†, Dae‑Wi Kim1,2†, Kihyun Lee1, Yong‑Seok Kim1, Hyo‑Young Oh3, You‑Hee Cho3 and Chang‑Jun Cha1*
1Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong 17456, Republic of Korea. 2Division of Life Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea. 3Department of Pharmacy, College of Pharmacy and Institute of Pharmaceuti‑cal Sciences, CHA University, Seongnam 13488, Republic of Korea.
†Do-Hoon Lee, Ju-Hee Cha, and Dae-Wi Kim contributed equally to this work.
*Correspondence
Abstract
Background
The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections.
Results
A bacterial strain of the Gram-negative opportunistic pathogen Stenotrophomonas maltophilia capable of degrading colistin and exhibiting a high-level colistin resistance was isolated from the soil environment. A colistin-degrading protease (Cdp) was identified in this strain, and its contribution to colistin resistance was demonstrated by growth inhibition experiments using knock-out (Δcdp) and complemented (Δcdp::cdp) mutants. Coculture and coinfection experiments revealed that S. maltophilia carrying the cdp gene could inactivate colistin and protect otherwise susceptible Pseudomonas aeruginosa, which may seriously affect the clinical efficacy of the drug for the treatment of cystic fibrosis patients with polymicrobial infection.
Conclusions
Our results suggest that Cdp should be recognized as a colistin resistance determinant that confers collective resistance at the microbial community level. Our study will provide vital information for successful clinical outcomes during the treatment of complex polymicrobial infections, particularly including S. maltophilia and other colistin-susceptible Gram-negative pathogens such as P. aeruginosa.
논문정보
관련 링크
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기