The Current State of Macrolide Resistance in Campylobacter spp.: Trends and Impacts of Resistance Mechanisms

Abstract

Campylobacter spp., especially Campylobacter jejuni and C. coli, are leading bacterial foodborne pathogens worldwide. In the United States, an estimated 0.8 million cases of campylobacteriosis occur annually, mostly involving C. jejuni Campylobacteriosis is generally self-limiting, but in severe cases, treatment with antibiotics may be mandated. The increasing incidence of fluoroquinolone resistance in Campylobacter has rendered macrolides such as erythromycin and azithromycin the drugs of choice for human campylobacteriosis. The prevalence of macrolide resistance in C. jejuni remains low, but macrolide resistance can be common in C. coli Substitutions in the 23S rRNA gene, specifically A2075G, and less frequently A2074C/G, remain the most common mechanism for high-level resistance to macrolides. In C. jejuni, resistance mediated by such substitutions is accompanied by a reduced ability to colonize chickens and other fitness costs, potentially contributing to the low incidence of macrolide resistance. Interestingly, similar fitness impacts have not been noted in C. coli Also noteworthy is a novel mechanism first reported in 2014 for a C. coli isolate from China and mediated by erm(B) harbored on multidrug resistance genomic islands. The incidence of erm(B) appears to reflect clonal expansion of certain strains, and whole-genome sequencing has been critical to the elucidation of erm(B)-associated macrolide resistance in Campylobacter spp. With the exception of one report from Spain, erm(B)-mediated macrolide resistance has been restricted to Campylobacter spp., mostly C. coli, of animal and human origin from China. If erm(B)-mediated macrolide resistance does not confer fitness costs in C. jejuni, the range of this gene may expand in C. jejuni, threatening to compromise treatment effectiveness for severe campylobacteriosis cases.

Keywords: Campylobacter; Campylobacter coli; Campylobacter jejuni; erm(B); erythromycin; macrolide; multidrug resistance; resistance.

FIG 1

The genetic environment of erm(B)-harboring MDRGIs in Campylobacter spp. Shaded regions indicate areas with greater than 98% identity. The erm(B) gene is shown in red, aminoglycoside resistance genes are shown in yellow, the tetracycline resistance gene tet(O) is shown in purple, genes with predicted functions are shown in green, and genes encoding hypothetical proteins are shown in white with bordering regions shown in black in accordance with previously published MDRGIs (25, 36, 37). The comparisons were performed using Geneious (version 9.1.4) (58). Deltas indicate deletions in the corresponding genes.