Adding to the family of resistance factors against last resort antibiotics: Identification and characterization of a novel carbapenemase, CIM-1

Yu Wang,Sylvia A. Sapula,Jonathan J. Whittall, Jack Blaikie, Olga Lomovskaya,Henrietta Venter

Research Square (Research Square)(2023)

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摘要
Abstract The increasing rate of carbapenem-resistant bacteria within healthcare environments is an issue of great concern that needs urgent attention. This resistance is driven by metallo-β-lactamases (MBLs), which can catalyse the hydrolysis of almost all clinically available β-lactams and are resistant to all the available β-lactamase inhibitors. In this study, a novel MBL was identified in a multidrug resistant isolate of the opportunistic pathogen, Chryseobacterium indologenes . Sequence analysis predicted this MBL (CIM-1) to be a lipoprotein with an atypical lipobox. Characterization of CIM-1 revealed it to be a membrane-associated, high-affinity carbapenemase with a broad spectrum of activity that includes all cephalosporins and carbapenems. This is the first report of the identification and characterisation of an MBL with an atypical lipobox and only the second lipidated MBL to be characterised after critically important NDM-1. We also identified more lipidated MBLs with non-canonical lipoboxes highlighting the necessity in further investigation of lipidated MBLs.
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novel carbapenemase,last resort antibiotics,resistance factors
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