Resveratrol Increases Sensitivity of Clinical Colistin-Resistant Pseudomonas aeruginosa to Colistin In Vitro and In Vivo

Lingbo Wang; Ying Zhang; Yishuai Lin; Jianming Cao; Chunyan Xu; Liqiong Chen; Yaran Wang; Yao Sun; Xiangkuo Zheng; Yong Liu; Tieli Zhou

doi:10.1128/spectrum.01992-22

Microbiology Spectrum (Feb 2023)

Resveratrol Increases Sensitivity of Clinical Colistin-Resistant Pseudomonas aeruginosa to Colistin In Vitro and In Vivo

Lingbo Wang,
Ying Zhang,
Yishuai Lin,
Jianming Cao,
Chunyan Xu,
Liqiong Chen,
Yaran Wang,
Yao Sun,
Xiangkuo Zheng,
Yong Liu,
Tieli Zhou

Affiliations

Lingbo Wang: Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People’s Republic of China
Ying Zhang: Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China
Yishuai Lin: Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China
Jianming Cao: Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China
Chunyan Xu: Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People’s Republic of China
Liqiong Chen: Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China
Yaran Wang: Wenzhou Institute, University of Chinese Academy of Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, China
Yao Sun: Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People’s Republic of China
Xiangkuo Zheng: Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People’s Republic of China
Yong Liu: Wenzhou Institute, University of Chinese Academy of Sciences, Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang, China
Tieli Zhou: Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People’s Republic of China

DOI: https://doi.org/10.1128/spectrum.01992-22
Journal volume & issue: Vol. 11, no. 1

Abstract

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ABSTRACT Infections caused by colistin-resistant P. aeruginosa strains pose a serious threat to public health. It is therefore urgent to find new strategies to deal with these bacterial infections. We aimed to investigate the efficacy and mechanisms of the colistin/resveratrol combination in eradicating colistin-resistant P. aeruginosa isolates and their biofilms both in vitro and in vivo. The results revealed that six clinically isolated colistin-resistant P. aeruginosa strains were multidrug resistant (MDR) strains, and resveratrol showed no antimicrobial activity against eight P. aeruginosa strains. Checkerboard assay and time-kill assays indicated that the combination therapy of resveratrol and colistin indicated a remarkable synergistic effect in vitro, and biofilm assays and SEM indicated synergistic antibiofilm activity. Furthermore, this combination could efficiently eliminate MDR bacteria in a murine infection model and improve the survival rate of Galleria mellonella. Fluorescence analysis, ALP, and β-galactosidase activity test results indicated that the colistin/resveratrol combination increased the membrane permeability of bacteria. In conclusion, our results may provide an efficient alternative pathway against colistin-resistant P. aeruginosa infections. IMPORTANCE P. aeruginosa is a ubiquitous Gram-negative opportunistic pathogen associated with a wide array of life-threatening acute and chronic infections. However, the improper and excessive use of antibiotics has contributed to the increasing emergence of multidrug-resistant (MDR) P. aeruginosa, even colistin-resistant strains, which presents a major challenge to clinical anti-infection treatment. Resveratrol, a naturally occurring polyphenolic antioxidant, can effectively slow down or avoid the occurrence and development of bacterial resistance and is expected to offer a promising strategy to overcome bacterial infections. In this study, colistin/resveratrol combination could synergistically damage the bacterial cell membrane, thereby inducing cell lysis while addressing the emergence of drug resistance. Moreover, this combination therapy may provide an efficient alternative pathway to combat the colistin-resistant P. aeruginosa in clinical practice.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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