Undetectable Production of the VIM-1 Carbapenemase in an Clinical Isolate.

The differential expression of VIM-1 in WEB-2 and ssp. WEB-1 clinical isolates from a rectal swab of a hospitalized patient in France was investigated. WEB-2 was resistant to all β-lactams except carbapenems. It produced ESBL SHV-12, but the Carba NP test failed to detect any carbapenemase activity despite the production of VIM-1. Conversely, WEB-1, previously recovered from the same patient, was positive for the detection of carbapenemase activity. The gene was located on a plasmid and embedded within class 1 integron. Both plasmids were of the same IncA incompatibility group and conferred the same resistance pattern when electroporated in TOP10 or CIP7933. Quantitative RT-PCR experiments indicated a weaker replication of pWEB-2 in as compared to . An isogenic mutant of WEB-2 selected after sequential passages with increased concentrations of imipenem possessed higher MICs for carbapenems and cephalosporins including cefiderocol, higher levels of the gene transcripts, and detectable carbapenemase activity using the Carba NP test. Assessment of read coverage demonstrated that a duplication of the region surrounding gene occurred in the mutant with detectable carbapenemase activity. The lack of detection of the VIM-1 carbapenemase activity in WEB-2 isolate was likely due to a weak replication of the IncA plasmid harboring the gene. Imipenem as selective pressure led to a duplication of this gene on the plasmid and to the restoration of a significant carbapenem-hydrolyzing phenotype.