Characterization of mutations in the rpoB gene associated with rifampin resistance in Rhodococcus equi isolated from foals.
Abstract: Treatment with a combination of erythromycin and rifampin has considerably improved survival rates of foals and immunocompromised patients suffering from severe pneumonia caused by Rhodococcus equi. Frequently, because of monotherapy, emergence of rifampin-resistant strains has been responsible for treatment failure. Using consensus oligonucleotides, we have amplified and sequenced the rifampin resistance (Rif(r))-determining regions of 12 rifampin-resistant R. equi strains isolated from three foals and of mutants selected in vitro from R. equi ATCC 3701, a rifampin-susceptible strain. The deduced amino acid sequences compared to those of four rifampin-susceptible R. equi strains showed several types of mutations. In 3 of the 10 strains isolated from one foal, His526Asn (Escherichia coli numbering) and Asp516Val mutations were associated with low-level resistance (rifampin MIC, 2 to 8 microg/ml), whereas His526Asp conferred high-level resistance (rifampin MIC, 128 microg/ml) in the 7 remaining strains. In strains from the two other foals, His526Asp and Ser531Leu mutations were found to be associated with high-level and low-level resistance, respectively. The in vitro mutants, highly resistant to rifampin, harbored His526Tyr and His526Arg substitutions. As described in other bacterial genera, His526, Ser531, and Asp516 are critical residues for rifampin resistance in R. equi, and the resistance levels are dependent on both the location and the nature of the substitution.
Publication Date: 2001-07-28 PubMed ID: 11473992PubMed Central: PMC88239DOI: 10.1128/JCM.39.8.2784-2787.2001Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on studying and characterizing mutations in the rpoB gene present in Rhodococcus equi which are known to create resistance to rifampin, an antibiotic mainly used for treating pneumonia in foals and immunocompromised patients.
Understanding the Research Context
- Rhodococcus equi is a bacterium causing severe pneumonia in foals and immunocompromised patients. It is often treated with a combination of erythromycin and rifampin.
- Rifampin-resistant strains of R. equi have emerged, due to monotherapy, leading to treatment failures.
- This study investigates the nature and impact of rpoB gene mutations contributing to rifampin resistance in R. equi.
Methodology and Findings
- The researchers amplified and sequenced the Rifampin resistance-determining regions of 12 rifampin-resistant R. equi strains isolated from three foals. These were then compared with four rifampin-susceptible R. equi strains.
- They identified several types of mutations. In 3 of the 10 strains isolated from one foal, His526Asn and Asp516Val mutations were associated with low-level resistance to rifampin, while His526Asp conferred high-level resistance in the remaining seven strains.
- In strains from two other foals, His526Asp and Ser531Leu mutations were associated with high and low-level resistance, respectively.
Conclusion and Relevance
- In vitro mutants highly resistant to rifampin carried His526Tyr and His526Arg substitutions.
- As seen in previous studies on other bacterial genera, His526, Ser531, and Asp516 are critical residues for rifampin resistance in R. equi.
- The resistance levels depend on both the location and nature of the substitution.
- A better understanding of these mutations could aid in developing effective treatments for Rhodococcus equi-induced pneumonia.
Cite This Article
APA
Fines M, Pronost S, Maillard K, Taouji S, Leclercq R.
(2001).
Characterization of mutations in the rpoB gene associated with rifampin resistance in Rhodococcus equi isolated from foals.
J Clin Microbiol, 39(8), 2784-2787.
https://doi.org/10.1128/JCM.39.8.2784-2787.2001 Publication
Researcher Affiliations
- Service de Microbiologie, CHU Côte de Nacre, 14033 Caen Cedex, France. fines-m@chu-caen.fr
MeSH Terms
- Actinomycetales Infections / microbiology
- Actinomycetales Infections / veterinary
- Animals
- Antibiotics, Antitubercular / pharmacology
- DNA-Directed RNA Polymerases / genetics
- Drug Resistance, Bacterial / genetics
- Horse Diseases / microbiology
- Horses
- Microbial Sensitivity Tests
- Mutation
- Pneumonia, Bacterial / microbiology
- Pneumonia, Bacterial / veterinary
- Rhodococcus equi / drug effects
- Rhodococcus equi / genetics
- Rifampin / pharmacology
- Sequence Analysis, DNA
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Citations
This article has been cited 14 times.- Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA. Antimicrobial Resistance Spectrum Conferred by pRErm46 of Emerging Macrolide (Multidrug)-Resistant Rhodococcus equi. J Clin Microbiol 2021 Sep 20;59(10):e0114921.
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