Effect of Macrolide and Rifampin Resistance on Fitness of Rhodococcus equi during Intramacrophage Replication and In Vivo.
Abstract: The soil-dwelling, saprophytic actinomycete is a facultative intracellular pathogen of macrophages and causes severe bronchopneumonia when inhaled by susceptible foals. Standard treatment for disease is dual-antimicrobial therapy with a macrolide and rifampin. Thoracic ultrasonography and early treatment with antimicrobials prior to the development of clinical signs are used as means of controlling endemic infection on many farms. Concurrently with the increased use of macrolides and rifampin for chemoprophylaxis and the treatment of subclinically affected foals, a significant increase in the incidence of macrolide- and rifampin-resistant isolates has been documented. Previously, our laboratory demonstrated decreased fitness of strains that were resistant to macrolides, rifampin, or both, resulting in impaired growth in iron-restricted media and in soil. The objective of this study was to examine the effect of macrolide and/or rifampin resistance on intracellular replication of in equine pulmonary macrophages and in an mouse infection model in the presence and absence of antibiotics. In equine macrophages, the macrolide-resistant strain did not increase in bacterial numbers over time and the dual macrolide- and rifampin-resistant strain exhibited decreased proliferation compared to the susceptible isolate. In the mouse model, in the absence of antibiotics, the susceptible isolate outcompeted the macrolide- or rifampin-resistant strains.
Copyright © 2019 American Society for Microbiology.
Publication Date: 2019-09-19 PubMed ID: 31331959PubMed Central: PMC6759311DOI: 10.1128/IAI.00281-19Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines the impact of resistance to two types of antibiotics – macrolides and rifampin – on the fitness of a bacteria strain, Rhodococcus equi, during its replication within macrophages and in an in-vivo mouse model. The study suggests that the resistant strains are less competitive than the susceptible ones.
Background and Purpose
- Rhodococcus equi is a soil-dwelling, actinomycete bacteria that, upon inhalation, can cause severe bronchopneumonia in foals. Standard treatment for this illness involves dual-antimicrobial therapy with a macrolide and rifampin.
- However, with increased use of these antibiotics for both prophylaxis and treatment, there has been a significant rise in R. equi strains resistant to them. The objective of this study was therefore to assess the effect of this resistance on the intracellular replication of R. equi in equine pulmonary macrophages, and also in a live mouse infection model, both in the presence and absence of antibiotics.
Methods and Findings
- To investigate the effect of antibiotic resistance on the bacteria’s fitness, researchers exposed R. equi to equine macrophages and studied the rate of bacterial proliferation in resistant vs. susceptible strains. Surprisingly, they found that the macrolide-resistant strain did not increase in bacterial numbers over time, and the strain resistant to both macrolide and rifampin also showed decreased proliferation compared to the susceptible isolate.
- The same study was repeated in a live mouse model, and similar results were observed. In the absence of antibiotics, the susceptible R. equi isolate outperformed the macrolide- or rifampin-resistant strains. This implies a decreased ‘competitive fitness’ of these resistant strains.
Implications of the Research
- While the development of drug-resistant strains of bacteria often raises the concern of hard-to-treat infections, these findings suggest a potential silver lining. The resistant strains of R. equi appear to be less ‘fit,’ showing a diminished ability to proliferate as compared to the antibiotic-susceptible strains.
- These findings deepen our understanding of how antibiotic resistance affects the fitness and proliferation of R. equi, and may shed light on ways to better manage or treat related infections in the future.
Cite This Article
APA
Willingham-Lane JM, Berghaus LJ, Berghaus RD, Hart KA, Giguère S.
(2019).
Effect of Macrolide and Rifampin Resistance on Fitness of Rhodococcus equi during Intramacrophage Replication and In Vivo.
Infect Immun, 87(10), e00281-19.
https://doi.org/10.1128/IAI.00281-19 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
- Actinomycetales Infections / drug therapy
- Actinomycetales Infections / immunology
- Actinomycetales Infections / microbiology
- Animals
- Anti-Bacterial Agents / pharmacology
- Clarithromycin / pharmacology
- Colony Count, Microbial
- Drug Resistance, Bacterial
- Genetic Fitness / drug effects
- Genetic Fitness / physiology
- Horses
- Liver / drug effects
- Liver / microbiology
- Lung / drug effects
- Lung / microbiology
- Macrophages, Alveolar / drug effects
- Macrophages, Alveolar / microbiology
- Male
- Mice
- Mice, Nude
- Microbial Sensitivity Tests
- Primary Cell Culture
- Rhodococcus equi / drug effects
- Rhodococcus equi / physiology
- Rifampin / pharmacology
- Spleen / drug effects
- Spleen / microbiology
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Citations
This article has been cited 2 times.- Álvarez-Narváez S, Huber L, Giguère S, Hart KA, Berghaus RD, Sanchez S, Cohen ND. Epidemiology and Molecular Basis of Multidrug Resistance in Rhodococcus equi. Microbiol Mol Biol Rev 2021 May 19;85(2).
- Huguet A-S, Gourbeyre O, Bousquet-Mélou A, Ferran AA, Lallemand EA. Reassessment of extracellular and intracellular activity of macrolides, rifampicin, and doxycycline against Rhodococcus equi based on bacterial counts and microscopy. Microbiol Spectr 2025 Sep 2;13(9):e0120525.
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