2. Academic Validation
  3. Effect of piperine on the inhibitory potential of MexAB-OprM efflux pump and imipenem resistance in carbapenem-resistant Pseudomonas aeruginosa

Effect of piperine on the inhibitory potential of MexAB-OprM efflux pump and imipenem resistance in carbapenem-resistant Pseudomonas aeruginosa

  • Microb Pathog. 2023 Oct 16:106397. doi: 10.1016/j.micpath.2023.106397.
Ying Liu 1,  Rui Zhu 2,  Xinwei Liu 3,  Dengzhou Li 2,  Mengyu Guo 4,  Bing Fei 4,  Yanying Ren 4,  Xiaojuan You 5,  Yongwei Li 6
Affiliations

Affiliations

  • 1 The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China; Henan Engineering Research Center for Identification of Pathogenic Microbes, Zhengzhou, 450002, China.
  • 2 The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China; The Key Laboratory of Pathogenic Microbes &Antimicrobial Resistance Surveillance of Zhengzhou, Zhengzhou, 450002, China; Henan Engineering Research Center for Identification of Pathogenic Microbes, Zhengzhou, 450002, China.
  • 3 The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China; Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450002, China; The Key Laboratory of Pathogenic Microbes &Antimicrobial Resistance Surveillance of Zhengzhou, Zhengzhou, 450002, China; Henan Engineering Research Center for Identification of Pathogenic Microbes, Zhengzhou, 450002, China; Henan Provincial Key Laboratory of Antimicrobials-Resistant Bacterial Infection Prevention & Therapy with Traditional Chinese Medicine, Zhengzhou, 450002, China.
  • 4 The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China; Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450002, China.
  • 5 The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China; Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450002, China; The Key Laboratory of Pathogenic Microbes &Antimicrobial Resistance Surveillance of Zhengzhou, Zhengzhou, 450002, China; Henan Engineering Research Center for Identification of Pathogenic Microbes, Zhengzhou, 450002, China. Electronic address: 632442656@qq.com.
  • 6 The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China; Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450002, China; The Key Laboratory of Pathogenic Microbes &Antimicrobial Resistance Surveillance of Zhengzhou, Zhengzhou, 450002, China; Henan Engineering Research Center for Identification of Pathogenic Microbes, Zhengzhou, 450002, China; Henan Provincial Key Laboratory of Antimicrobials-Resistant Bacterial Infection Prevention & Therapy with Traditional Chinese Medicine, Zhengzhou, 450002, China. Electronic address: lyw@hactcm.edu.cn.
PMID: 37852553 DOI: 10.1016/j.micpath.2023.106397
Abstract

The escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to global public health through the spread of its 'high-risk' clones. Immediate and decisive research into antimicrobial agents against CRPA is crucial for the development of effective measures and interventions. Overexpression of the MexAB-OprM efflux pump is one of the major mechanisms of CRPA. Since the active efflux of Antibacterial agents plays a significant role in mediating drug resistance in CRPA, the inhibition of efflux pumps has become a promising strategy to restore Antibacterial potency. Piperine (PIP) has been proven to be a promising efflux pump inhibitor in some bacteria. However, there are no studies on whether PIP can act as a potential efflux pump inhibitor in CRPA. The present study aimed to identify the Antibacterial activity of PIP against CRPA and to evaluate the effect on the MexAB-OprM efflux pump. Molecular docking was used to analyze the possible interaction of PIP with the proteins of the MexAB-OprM efflux pump in CRPA. The effect of PIP on the expression of the MexAB-OprM efflux pump was investigated by real-time quantitative PCR (qPCR) and ethidium bromide accumulation efflux assay. The effect of PIP on CRPA imipenem (IPM) resistance was investigated by the checkerboard dilution method. The results demonstrated that PIP exhibited the lowest binding affinity of -9.1 kcal towards efflux pump proteins. A synergistic effect between PIP and IPM on CRPA was observed. More importantly, PIP effectively hindered the efflux of ethidium bromide and IPM by up-regulating MexR gene expression while down-regulating MexA, MexB, and OprM gene expressions. In conclusion, PIP could enhance the Antibacterial activity of IPM by inhibiting the MexAB-OprM efflux pump. Our work proved that PIP had the potential to be an efflux pump inhibitor of CRPA.

Keywords

Carbapenem-resistant Pseudomonas aeruginosa; Imipenem; MexAB-OprM efflux pump; Piperine.

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