Emergence of multidrug-resistant Campylobacter species isolates with a horizontally acquired rRNA methylase

Abstract

Antibiotic-resistant Campylobacter constitutes a serious threat to public health, and resistance to macrolides is of particular concern, as this class of antibiotics is the drug of choice for clinical therapy of campylobacteriosis. Very recently, a horizontally transferrable macrolide resistance mediated by the rRNA methylase gene erm(B) was reported in a Campylobacter coli isolate, but little is known about the dissemination of erm(B) among Campylobacter isolates and the association of erm(B)-carrying isolates with clinical disease. To address this question and facilitate the control of antibiotic-resistant Campylobacter, we determined the distribution of erm(B) in 1,554 C. coli and Campylobacter jejuni isolates derived from food-producing animals and clinically confirmed human diarrheal cases. The results revealed that 58 of the examined isolates harbored erm(B) and exhibited high-level resistance to macrolides, and most were recent isolates, derived in 2011-2012. In addition, the erm(B)-positive isolates were all resistant to fluoroquinolones, another clinically important antibiotic used for treating campylobacteriosis. The erm(B) gene is found to be associated with chromosomal multidrug resistance genomic islands (MDRGIs) of Gram-positive origin or with plasmids of various sizes. All MDRGIs were transferrable to macrolide-susceptible C. jejuni by natural transformation under laboratory conditions. Molecular typing of the erm(B)-carrying isolates by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) identified diverse genotypes and outbreak-associated diarrheal isolates. Molecular typing also suggested zoonotic transmission of erm(B)-positive Campylobacter. These findings reveal an emerging and alarming trend of dissemination of erm(B) and MDRGIs in Campylobacter and underscore the need for heightened efforts to control their further spread.

FIG 1

Chromosomal organization and comparison of six different types (I to VI) of MDRGIs in erm(B)-positive C. coli isolates. erm(B) is in red, aminoglycoside resistance genes are in yellow, the streptothricin resistance gene (sat4) is in blue, the tetracycline resistance gene [tet(O)] is in purple, genes with predicted functions are in green, and genes coding hypothetical proteins are in white. The tet(O) gene is intact in types V and VI but is truncated in other types. The border genes of the MDRGIs are depicted by black box arrows. The gray shading indicates regions sharing more than 98% DNA identity. A representative strain for each type of MDRGIs is indicated on the right of the panel.

FIG 2

PFGE and MLST typing of 58 erm(B)-positive C. coli isolates. STs 5923, 5943, 5946, 5948, 6073, 6074, and 6075 were newly designated in this study. SmaI was used for PFGE. Provinces and cities include Shandong (SD), Ningxia (NX), Guangdong (GD), Henan (HN), and Shanghai (SH). Sources and host species include swine (S), chicken (C), chicken carcasses (CC), duck (D), and human (H). −, a clonal complex cannot be assigned.