Characterization of the Multi-Drug Resistance Gene cfr in Methicillin-Resistant Staphylococcus aureus (MRSA) Strains Isolated From Animals and Humans in China

Abstract

We investigated <i>cfr</i>-positive and -negative MRSA strains isolated from animals and humans in different geographical areas of China, from 2011 to 2016. Twenty <i>cfr</i>-positive strains (15.6%) were identified from 128 MRSA strains including 17 from food animals and three from humans. The resistance rates and prevalence of the tested antibiotic resistance genes (ARGs) in the <i>cfr</i>-positive MRSA isolates were higher than that in the <i>cfr</i>-negative MRSA isolates. All <i>cfr</i>-positive MRSA isolates were co-carrying <i>fexA</i> and <i>ermC</i>, and had significantly higher <i>optrA</i> incidence rate vs. the <i>cfr</i>-negative isolates (<i>P</i> < 0.05). In addition, multilocus sequence typing (MLST) assays showed that ST9 and <i>spa</i>-type t899 were the most prevalent ST and <i>spa</i> types in the study strains. However, all of the 20 <i>cfr</i>-positive and 10 randomly selected <i>cfr</i>-negative MRSA isolates were clonally unrelated as determined by pulsed-field gel electrophoresis (PFGE) analyses. Importantly, the <i>cfr</i> gene was successfully transferred to a recipient <i>Staphylococcus aureus</i> strain RN4220 from 13 of the 20 <i>cfr</i>-positive MRSA isolates by electroporation. Among these 13 <i>cfr</i>-positive MRSA isolates, two different genetic contexts surrounding <i>cfr</i> were determined and each was associated with one type of <i>cfr</i>-carrying plasmids. Of note, the predominant genetic context of <i>cfr</i> was found to be a Tn<i>558</i> variant and locate on large plasmids (∼50 kb) co-harboring <i>fexA</i> in 11 of the 13 MRSA isolates. Furthermore, the <i>cfr</i> gene was also identified on small plasmids (∼ 7.1 kb) that co-carried <i>ermC</i> in two of the 13 MRSA isolates. Our results demonstrated a high occurrence of multi-drug resistance in <i>cfr</i>-positive MRSA isolates, and the spread of <i>cfr</i> might be attributed to horizontal dissemination of similar <i>cfr</i>-carrying transposons and plasmids.