Glabridin inhibited the spread of polymyxin-resistant Enterobacterium carrying ICEMP63.

Introduction: The role of integrative and conjugative elements (ICEs) in antibiotic resistance in is unknown. This study aimed to determine whether an ICE identified in the 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 , 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 ICEMP63, was identified. ICEMP63 was verified to be horizontally transferred among Enterobacteriaceae bacteria. G3577_03020 in ICEMP63 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 ICEMP63 in Enterobacteriaceae bacteria. Combined glabridin and polymyxin may have therapeutic potential for treating infections from multi-drug resistant bacteria carrying ICEMP63.