Genomic insights into Colistin Resistant Klebsiella pneumoniae from a Tunisian teaching hospital [PublishAheadOfPrint]

The emergence of colistin-resistant Klebsiella pneumoniae (CoRKp) is a public health concern since this antibiotic has become the last line of treatment for infections caused by multidrug-resistant (MDR) gram-negatives. In this study, we have investigated the molecular basis of colistin-resistance in 13 MDR Kp isolated from 12 patients in a teaching hospital in Sousse, Tunisia. Whole-genome sequencing (WGS) was used to decipher the molecular mechanism of colistin-resistance and to identify the resistome of these CoRKp. It revealed a genome of ca. 5,5 Mbp in size with a G+C content of 57% corresponding to that commonly observed for K. pneumoniae. These isolates belonged the 5 different STs (ST11, ST15, ST101, ST147, and ST392) and their resistome was composed of acquired β-lactamases including ESBLs and carbapenemases (bla_CTX-M-15, bla_OXA-204, bla_OXA-48, bla_NDM-1 genes), aminoglycoside resistance genes (aac(6')Ib-cr, aph(3' ')-Ib, aph(6)-Id, aac(3)-IIa), fosfomycin (fosA), fluoroquinolone (qnr-like), chloramphenicol, trimethoprim and tetracyclin resistance genes. All the isolates were identified as having a mutated mgrB gene. Mapping reads with reference sequences of the most common genes involved in colistin-resistance revealed several modifications in mgrB, pmr and pho operons (deletions, insertion, susbstitution, ..) likely affecting the function of these proteins. Noteworthy, among the 12 patients, 10 were treated with colistin before the isolation of CoRKp. No plasmid encoding mcr-1-5 genes were found in these isolates.

This study corresponds to the first molecular characterization of a collection of CoRKp in Tunisia, and highlights that the small transmembrane protein MgrB is a main mechanism for colistin resistance in K. pneumoniae.

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