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Glabridin inhibited the spread of polymyxin-resistant Enterobacterium carrying ICE
Jiafang Fu1,2, Yayu Liu1,2, Fengtian Wang3
1First 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.
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.
Insights
A novel integrative and conjugative element (ICE), ICEMmoMP63, was identified in Morganella morganii, conferring polymyxin resistance. This ICE can transfer between bacteria, and glabridin may inhibit polymyxin resistance.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Integrative and conjugative elements (ICEs) are mobile genetic elements with largely unknown roles in antibiotic resistance in Morganella morganii.
- Polymyxin resistance is a growing public health concern, necessitating research into its genetic underpinnings.
Purpose of the Study:
- To investigate the contribution of an identified ICE in M. morganii to polymyxin resistance.
- To determine the transferability and mechanisms of antibiotic resistance conferred by the ICE.
Main Methods:
- Whole-genome sequencing and bioinformatics analyses were used to identify ICEs and antibiotic resistance genes.
- Conjugation assays and heterologous expression in Escherichia coli were performed to assess ICE transferability and function.
- Minimum inhibitory concentrations were determined, and a traditional Chinese medicine library was screened for efflux pump inhibitors.
Main Results:
- An ICE, designated ICEMmoMP63, was identified and confirmed to be horizontally transferable among Enterobacteriaceae.
- A gene (G3577_03020) on ICEMmoMP63 was found to mediate multiple antibiotic resistances, particularly to polymyxins.
- The natural compound glabridin demonstrated inhibitory effects on polymyxin resistance.
Conclusions:
- Monitoring the dissemination of ICEMmoMP63 in Enterobacteriaceae is crucial due to its role in antibiotic resistance.
- Combination therapy with glabridin and polymyxin shows potential for treating infections caused by multi-drug resistant bacteria carrying ICEMmoMP63.
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