AUTHOR=Jousset Agnès B. , Rosinski-Chupin Isabelle , Takissian Julie , Glaser Philippe , Bonnin Rémy A. , Naas Thierry 

TITLE=Transcriptional Landscape of a blaKPC-2 Plasmid and Response to Imipenem Exposure in Escherichia coli TOP10

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.02929

DOI=10.3389/fmicb.2018.02929

ISSN=1664-302X

ABSTRACT=<p>The diffusion of KPC-2 carbapenemase is closely related to the spread of <italic>Klebsiella pneumoniae</italic> of the clonal-group 258 and linked to IncFII<sub>K</sub> plasmids. Little is known about the biology of multi-drug resistant plasmids and the reasons of their successful dissemination. Using <italic>E. coli</italic> TOP10 strain harboring a multi-replicon IncFII<sub>K</sub>-IncFIB <italic>bla</italic><sub>KPC−2</sub>-gene carrying plasmid pBIC1a from <italic>K. pneumoniae</italic> ST-258 clinical isolate BIC-1, we aimed to identify basal gene expression and the effects of imipenem exposure using whole transcriptome approach by RNA sequencing (RNA-Seq). Independently of the antibiotic pressure, most of the plasmid-backbone genes were expressed at low levels. The most expressed pBIC1a genes were involved in antibiotic resistance (<italic>bla</italic><sub>KPC−2</sub>, <italic>bla</italic><sub>TEM</sub> and <italic>aph</italic>(3′)-I), in plasmid replication and conjugation, or associated to mobile elements. After antibiotic exposure, 34% of <italic>E. coli</italic> (pBIC1a) genome was differentially expressed. Induction of oxidative stress response was evidenced, with numerous upregulated genes of the <italic>SoxRS/OxyR</italic> oxydative stress regulons, the Fur regulon (for iron uptake machinery), and <italic>IscR</italic> regulon (for iron sulfur cluster synthesis). Nine genes carried by pBIC1a were up-regulated, including the murein DD-endopeptidase <italic>mepM</italic> and the copper resistance operon. Despite the presence of a carbapenemase, we observed a major impact on <italic>E. coli</italic> (pBIC1a) whole transcriptome after imipenem exposure, but no effect on the level of transcription of antimicrobial resistance genes. We describe adaptive responses of <italic>E. coli</italic> to imipenem-induced stress, and identified plasmid-encoded genes that could be involved in resistance to stressful environments.</p>