Whole-Genome Sequence Analysis of Multidrug-Resistant Campylobacter Isolates: a Focus on Aminoglycoside Resistance Determinants

Abstract

A whole-genome sequencing (WGS) approach was conducted in order to identify the molecular determinants associated with antimicrobial resistance in 12 multidrug-resistant <i>Campylobacter jejuni</i> and <i>Campylobacter coli</i> isolates, with a focus on aminoglycoside resistance determinants. Two variants of a new aminoglycoside phosphotransferase gene [<i>aph</i>(<i>2</i>″)-<i>Ii₁</i> and <i>aph</i>(<i>2</i>″)-<i>Ii₂</i> ] putatively associated with gentamicin resistance were found. In addition, the following new genes were identified for the first time in <i>Campylobacter</i>: a lincosamide nucleotidyltransferase gene [<i>lnu</i>(G)], likely associated with lincomycin resistance, and two resistance enzyme genes (<i>spw</i> and <i>apmA</i>) similar to those found in <i>Staphylococcus aureus</i>, which may confer spectinomycin and gentamicin resistance, respectively. A C1192T mutation of the 16S rRNA gene that may be involved in spectinomycin resistance was also found in a <i>C. coli</i> isolate. Genes identified in the present study were located either on the bacterial chromosome or on plasmids that could be transferred naturally. Their role in aminoglycoside resistance remains to be supported by genetic studies. Regarding the other antimicrobial agents studied, i.e., ampicillin, ciprofloxacin, erythromycin, and tetracycline, a perfect correlation between antimicrobial phenotypes and genotypes was found. Overall, our data suggest that WGS analysis is a powerful tool for identifying resistance determinants in <i>Campylobacter</i> and can disclose the full genetic elements associated with resistance, including antimicrobial compounds not tested routinely in antimicrobial susceptibility testing.