ABSTRACTRhodococcus equiis a leading cause of severe pneumonia in foals. Standard treatment is dual antimicrobial therapy with a macrolide and rifampin, but the emergence of macrolide- and rifampin-resistantR. equiisolates is an increasing problem. The objective of this study was to determine the effect of macrolide and/or rifampin resistance on fitness ofR. equi. Three unique isogenic sets were created, each consisting of fourR. equistrains, as follows: a susceptible parent isolate, strains resistant to macrolides or rifampin, and a dual macrolide- and rifampin-resistant strain. Each isogenic set’s bacterial growth curve was generated in enriched medium, minimal medium (MM), and minimal medium without iron (MM-I). Bacterial survival in soil was analyzed over 12 months at −20°C, 4°C, 25°C, and 37°C, and the ability of these strains to retain antimicrobial resistance during sequential subculturing was determined. Insertion of the mobile element conferring macrolide resistance had minimal effect onin vitrogrowth. However, two of threerpoBmutations conferring rifampin resistance resulted in a decreased growth rate in MM. In soil, macrolide- or rifampin-resistantR. equistrains exhibited limited growth compared to that of the susceptibleR. equiisolate at all temperatures except −20°C. During subculturing, macrolide resistance was lost over time, and two of threerpoBmutations reverted to the wild-type form. The growth of rifampin-resistantR. equicolonies is delayed under nutrient restriction. In soil, possession of rifampin or macrolide resistance results in decreased fitness. Both macrolide and rifampin resistance can be lost after repeated subculturing.IMPORTANCEThis work advances our understanding of the opportunistic environmental pathogenRhodococcus equi, a disease agent affecting horses and immunocompromised people.R. equiis one of the most common causes of severe pneumonia in young horses. For decades, the standard treatment forR. equipneumonia in horses has been dual antimicrobial therapy with a macrolide and rifampin; effective alternatives to this combination are lacking. The World Health Organization classifies these antimicrobial agents as critically important for human medicine. Widespread macrolide and rifampin resistance inR. equiisolates is a major emerging problem for the horse-breeding industry and might also adversely impact human health if resistant strains infect people or transfer resistance mechanisms to other pathogens. This study details the impact of antimicrobial resistance onR. equifitness, a vital step for understanding the ecology and epidemiology of resistantR. equiisolates, and will support development of novel strategies to combat antimicrobial resistance.
Antimicrobial resistance in Rhodococcus equi.
