Effect of Macrolide and Rifampin Resistance on the Fitness of Rhodococcus equi.
Abstract: is 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-resistant isolates is an increasing problem. The objective of this study was to determine the effect of macrolide and/or rifampin resistance on fitness of Three unique isogenic sets were created, each consisting of four strains, 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 on growth. However, two of three mutations conferring rifampin resistance resulted in a decreased growth rate in MM. In soil, macrolide- or rifampin-resistant strains exhibited limited growth compared to that of the susceptible isolate at all temperatures except -20°C. During subculturing, macrolide resistance was lost over time, and two of three mutations reverted to the wild-type form. The growth of rifampin-resistant colonies 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. This work advances our understanding of the opportunistic environmental pathogen , a disease agent affecting horses and immunocompromised people. is one of the most common causes of severe pneumonia in young horses. For decades, the standard treatment for pneumonia 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 in isolates 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 on fitness, a vital step for understanding the ecology and epidemiology of resistant isolates, and will support development of novel strategies to combat antimicrobial resistance.
Copyright © 2019 American Society for Microbiology.
Publication Date: 2019-03-22 PubMed ID: 30683740PubMed Central: PMC6585491DOI: 10.1128/AEM.02665-18Google Scholar: Lookup
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- Journal Article
Summary
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This study explores the impact of resistance to macrolide and rifampin, two antibiotics, on the fitness of the bacterium Rhodococcus equi, which is often a cause of severe pneumonia in young horses. The research indicates that the acquired resistance can lessen the robustness of the bacteria in certain conditions and may also be lost over time.
Research Methodology
- The researchers created three sets of Rhodococcus equi strains. In each set, there were four variants of the bacteria: the regular bacteria, bacteria resistant to macrolide, bacteria resistant to rifampin, and one resistant to both macrolide and rifampin.
- Growth rate of each strain was measured in various mediums including enriched medium, minimal medium (MM), and minimal medium without iron (MM-I).
- The survival rate of these strains was also tracked over the course of a year in soil at different temperatures.
- The team further monitored if these strains maintained their antibiotic resistance through multiple growth cycles, via sequential subculturing.
Key Findings
- Resistance to macrolide, brought about by the insertion of a mobile element into the bacteria, had minimal effect on the growth of Rhodococcus equi.
- However, the mutations that caused rifampin resistance in two out of three sets slowed down the bacteria’s growth in MM.
- The researchers also observed that in soil, Rhodococcus equi strains resistant to macrolide or rifampin had limited growth at all temperatures, except at -20°C, when compared to the non-resistant strain.
- Over time, during the process of sequential subculturing, resistance to macrolide was lost. Also, in two out of three sets, the rifampin-resistant mutations reverted to the original, non-resistant form.
Implications of the Study
- This research enhances our understanding of Rhodococcus equi’s behavior. This microbe is not only a significant cause of pneumonia in foals but is also dangerous to humans with compromised immunity.
- The findings of the study could aid in the development of new strategies to battle antibiotic resistance in bacteria, which is alarming for both horse-rearing industry and human health.
Cite This Article
APA
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S.
(2019).
Effect of Macrolide and Rifampin Resistance on the Fitness of Rhodococcus equi.
Appl Environ Microbiol, 85(7), e02665-18.
https://doi.org/10.1128/AEM.02665-18 Publication
Researcher Affiliations
- Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA jmwlane1@gmail.com.
- Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
- Department of Population Health, University of Georgia, Athens, Georgia, USA.
- Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
- Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
MeSH Terms
- Animals
- Anti-Bacterial Agents / pharmacology
- Bacterial Proteins / genetics
- DNA-Directed RNA Polymerases / genetics
- Drug Resistance, Bacterial / drug effects
- Drug Resistance, Bacterial / genetics
- Horse Diseases / microbiology
- Horses
- Humans
- Macrolides / pharmacology
- Microbial Sensitivity Tests
- Rhodococcus equi / drug effects
- Rhodococcus equi / genetics
- Rhodococcus equi / growth & development
- Rifampin / pharmacology
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Citations
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