Cross-resistance to 14-, 15- and 16-membered ring macrolides in Salmonella and Campylobacter

Abstract

Objectives: This study aimed to gain a better understanding of how resistance determinants in Salmonella and Campylobacter contribute to 14-, 15- and 16-membered ring macrolide resistance phenotypes.

Methods: A total of 126 azithromycin-resistant (AziR) and -susceptible (AziS) [Salmonella (n = 45) and Campylobacter (n = 81)] isolates were selected for antimicrobial susceptibility testing (AST) and WGS.

Results: Seven functional macrolide resistance determinants, including erm(42), mef(C), mph(A), mph(E), mph(G), msr(E) and one point mutation (acrB_R717L) were previously identified in AziRSalmonella. These determinants resulted in an 8- and 16-fold 15-membered ring gamithromycin and azithromycin MIC50 increase, respectively, compared with AziS isolates, with a maximum MIC increase of up to 256. The same isolates also exhibited up to a 32-fold 14-membered ring erythromycin MIC50 increase. Salmonella with erm(42) or acrB_R717L showed up to 128-fold 16-membered ring macrolide tildipirosin MIC increase, compared with isolates that were susceptible or carrying other macrolide resistance genes. In Campylobacter, all AziR isolates had an MIC50 ranging from 32 to 4096 mg/L of the various membered ring macrolides, whereases all susceptible Campylobacter isolates had significantly lower MIC50 values, ranging from 0.25 to 4 mg/L. The MIC50 of the various ring macrolides for AziRCampylobacter isolates was 16- to 4096-fold higher when compared with AziSCampylobacter.

Conclusions: Our study has revealed that the function of macrolide resistance genes in Salmonella can be associated with specific macrolide ring structures, whereas the single 23S rRNA mutation in Campylobacter results in significantly elevated MICs of all macrolides. for the various ring macrolides.