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Free keywords:
antibiotic resistance; carbapenemases; clinically relevant bacteria; integrative and conjugative elements
Abstract:
Carbapenemases inactivate most β-lactam antibiotics, including carbapenems, and have frequently been reported among
Enterobacteriaceae, Acinetobacter spp. and Pseudomonas spp. Traditionally, the horizontal gene transfer of carbapenemaseencoding genes (CEGs) has been linked to plasmids. However, given that integrative and conjugative elements (ICEs) are possibly the most abundant conjugative elements among prokaryotes, we conducted an in silico analysis to ascertain the likely role
of ICEs in the spread of CEGs among all bacterial genomes (n=182663). We detected 17 520 CEGs, of which 66 were located
within putative ICEs among several bacterial species (including clinically relevant bacteria, such as Pseudomonas aeruginosa,
Klebsiella pneumoniae and Escherichia coli). Most CEGs detected within ICEs belong to the IMP, NDM and SPM metallo-betalactamase families, and the serine beta-lactamase KPC and GES families. Different mechanisms were likely responsible for
acquisition of these genes. The majority of CEG-bearing ICEs belong to the MPFG, MPFT
and MPFF
classes and often encode
resistance to other antibiotics (e.g. aminoglycosides and fluoroquinolones). This study provides a snapshot of the different CEGs
associated with ICEs among available bacterial genomes and sheds light on the underappreciated contribution of ICEs to the
spread of carbapenem resistance globally.