Glabridin inhibited the spread of polymyxin-resistant Enterobacterium carrying ICE Mmo MP63

Jiafang Fu; Yayu Liu; Fengtian Wang; Gongli Zong; Zhen Wang; Chuanqing Zhong; Guangxiang Cao

doi:10.3389/fmicb.2023.1188900

Glabridin inhibited the spread of polymyxin-resistant Enterobacterium carrying ICE Mmo MP63

Front Microbiol. 2023 May 22:14:1188900. doi: 10.3389/fmicb.2023.1188900. eCollection 2023.

Authors

Jiafang Fu^{1

2}, Yayu Liu^{1

2}, Fengtian Wang³, Gongli Zong^{1

2}, Zhen Wang⁴, Chuanqing Zhong⁴, Guangxiang Cao^{1

2}

Affiliations

¹ First Affiliated Hospital of Shandong First Medical University, Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
² National Health Commission (NHC) Key Laboratory of Biotechnology Drugs. Shandong Academy of Medical Sciences, Jinan, China.
³ Jinan Municipal Minzu Hospital, Jinan, China.
⁴ School of Municipal and Environmental Engineering, Shandong Jianzhu University, Jinan, China.

Abstract

Introduction: The role of integrative and conjugative elements (ICEs) in antibiotic resistance in Morganella morganii is unknown. This study aimed to determine whether an ICE identified in the M. morganii genome contributed to the polymyxin resistance.

Methods: Whole-genome sequencing was performed followed by bioinformatics analyses to identify ICEs and antibiotic resistance genes. Conjugation assays were performed to analyze the transferability of a discovered ICE. A drug transporter encoded on the ICE was heterogeneously expressed in Escherichia coli, minimum inhibitory concentrations of antibiotics were determined, and a traditional Chinese medicine library was screened for potential efflux pump inhibitors.

Results: An antibiotic resistance-conferring ICE, named ICEMmoMP63, was identified. ICEMmoMP63 was verified to be horizontally transferred among Enterobacteriaceae bacteria. G3577_03020 in ICEMmoMP63 was found to mediate multiple antibiotic resistances, especially polymyxin resistance. However, natural compound glabridin was demonstrated to inhibit polymyxin resistance.

Discussion: Our findings support the need for monitoring dissemination of ICEMmoMP63 in Enterobacteriaceae bacteria. Combined glabridin and polymyxin may have therapeutic potential for treating infections from multi-drug resistant bacteria carrying ICEMmoMP63.

Keywords: MFS transporter; Morganella morganii; glabridin; integrative and conjugative element; polymyxin resistance.

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Province (No. ZR2022MH107), the Key Research and Development Project of Shandong Province (No. 2021ZDSYS27), the Innovation Project of the Shandong Academy of Medical Sciences (No. 2022), and the Academic Promotion Programme of Shandong First Medical University (No. 2019LJ001).