AUTHOR=Girlich Delphine , Bonnin Rémy A. , Proust Alexis , Naas Thierry , Dortet Laurent 

TITLE=Undetectable Production of the VIM-1 Carbapenemase in an Atlantibacter hermannii Clinical Isolate

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.741972

DOI=10.3389/fmicb.2021.741972

ISSN=1664-302X

ABSTRACT=<p>The differential expression of VIM-1 in <italic>Atlantibacter hermannii</italic> WEB-2 and <italic>Enterobacter hormaechei</italic> ssp. <italic>hoffmannii</italic> WEB-1 clinical isolates from a rectal swab of a hospitalized patient in France was investigated. <italic>A. hermannii</italic> 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, <italic>E. hormaechei</italic> WEB-1, previously recovered from the same patient, was positive for the detection of carbapenemase activity. The <italic>bla</italic><sub>VIM–1</sub> 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 <italic>Escherichia coli</italic> TOP10 or <italic>Enterobacter cloacae</italic> CIP7933. Quantitative RT-PCR experiments indicated a weaker replication of pWEB-2 in <italic>A. hermannii</italic> as compared to <italic>E. hormaechei</italic>. An isogenic mutant of <italic>A. hermannii</italic> WEB-2 selected after sequential passages with increased concentrations of imipenem possessed higher MICs for carbapenems and cephalosporins including cefiderocol, higher levels of the <italic>bla</italic><sub>VIM–1</sub> gene transcripts, and detectable carbapenemase activity using the Carba NP test. Assessment of read coverage demonstrated that a duplication of the region surrounding <italic>bla</italic><sub>VIM–1</sub> gene occurred in the <italic>A. hermannii</italic> mutant with detectable carbapenemase activity. The lack of detection of the VIM-1 carbapenemase activity in <italic>A. hermannii</italic> WEB-2 isolate was likely due to a weak replication of the IncA plasmid harboring the <italic>bla</italic><sub>VIM–1</sub> 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.</p>