Genome-Wide Association Study Reveals Genetic Markers for Antimicrobial Resistance in Mycoplasma bovis

Bokma, Jade; Vereecke, Nick; Nauwynck, Hans; Haesebrouck, Freddy; Theuns, Sebastiaan; Pardon, Bart; Boyen, Filip

doi:10.1128/spectrum.00262-21

Cited by 30 publications

(19 citation statements)

References 51 publications

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“…A G748A mutation in both 23S rRNA alleles, as well as a Gln93His mutation in the rplv gene were found. In previous studies, G748A mutations have been observed in isolates resistant to tylosin and tilmicosin, whereas the Gln93His mutation has been linked to resistance against macrolides (gamithromycin and tylosin) when combined with a mutation in domain 5 of 1 or both 23S rRNA gene alleles on position A2058 36‐39 . In this case, no mutations on position A2058 were found.…”

Section: Resultsmentioning

confidence: 59%

“…In previous studies, G748A mutations have been observed in isolates resistant to tylosin and tilmicosin, whereas the Gln93His mutation has been linked to resistance against macrolides (gamithromycin and tylosin) when combined with a mutation in domain 5 of 1 or both 23S rRNA gene alleles on position A2058. [36][37][38][39] In this case, no mutations on position A2058 were found. Additionally, 1 new Lys184Asn mutation was found in the rpId gene.…”

Section: Laboratory Diagnosismentioning

confidence: 59%

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Randomized field trial comparing the efficacy of florfenicol and oxytetracycline in a natural outbreak of calf pneumonia using lung reaeration as a cure criterion

Jourquin

Bokma

Cremer

et al. 2022

Veterinary Internal Medicne

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Background Respiratory infections are the main indication for antimicrobial use in calves. Optimal treatment duration currently is unknown, but shorter duration would likely decrease selection for antimicrobial resistance. Hypothesis/Objectives Determine differences in cure rate and healing time between animals treated with florfenicol and oxytetracycline in a natural outbreak of respiratory disease using reaeration observed on thoracic ultrasound examination as healing criterion. Animals Commercial farm housing 130, 3 to 9 month old Belgian blue beef calves. Methods Randomized clinical trial during an outbreak of respiratory disease. Metaphylactic treatment was initiated, randomly treating animals with either florfenicol or oxytetracycline. Ultrasonographic follow‐up was done the first day and every other day for a 14‐day period. At the individual animal level, treatment was discontinued when reaeration of the lungs occurred. Differences in cure rate and healing time were determined. Results Of the 130 animals studied, 67.7% developed a lung consolidation ≥0.5 cm. The mean ultrasonographic healing time was 2.5 days in the florfenicol group compared to 3.1 days in the oxytetracycline group (P = .04). After single treatment, 80.6% and 60.3% had no consolidations in the florfenicol and oxytetracycline groups, respectively (P = .01). A Mycoplasma bovis strain was genetically and phenotypically determined to be susceptible to both antimicrobials. Conclusions and Clinical Importance Ultrasonographic lung reaeration shows potential as a cure criterion to rationalize antimicrobial use for outbreaks of pneumonia. In our study, florfenicol resulted in a faster cure and higher reduction in antimicrobial usage than did oxytetracycline.

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Section: Resultsmentioning

confidence: 59%

Section: Laboratory Diagnosismentioning

confidence: 59%

Randomized field trial comparing the efficacy of florfenicol and oxytetracycline in a natural outbreak of calf pneumonia using lung reaeration as a cure criterion

Jourquin

Bokma

Cremer

et al. 2022

Veterinary Internal Medicne

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“…The significant NVs linked to TIL resistance were primarily ABC transporters, giving credence to the idea of innate resistance through efflux pumps. Bokma et al also reported multiple ABC-type macrolide efflux pump genes [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…Only a few GWAS studies have been conducted to characterize AMR in M. bovis [ 26 , 27 ], which may be related to the technical expertise required in conducting such studies. Furthermore, a limitation of GWAS is the occurrence of false positive associations between the traits and genetic variants, commonly referred to as “ p -value inflation” [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although sample size requirements may differ depending on the variation of phenotypic traits, the number of DNA markers analyzed, and the purpose of the study, there is an underlying convention of having a minimum sample size of 100 bacterial isolates [ 32 , 33 , 34 ]. Bokma et al performed a combination GWAS and manual study of 95 M. bovis genomes to identify gene targets associated with AMR [ 27 ]. This analysis identified known NVs as well as novel variants associated with resistance to fluoroquinolones, macrolides, tetracyclines, and aminoglycosides.…”

Section: Introductionmentioning

confidence: 99%

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Genome-Wide Association Study of Nucleotide Variants Associated with Resistance to Nine Antimicrobials in Mycoplasma bovis

et al. 2022

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Antimicrobial resistance (AMR) studies of Mycoplasma bovis have generally focused on specific loci versus using a genome-wide association study (GWAS) approach. A GWAS approach, using two different models, was applied to 194 Mycoplasma bovis genomes. Both a fixed effects linear model (FEM) and a linear mixed model (LMM) identified associations between nucleotide variants (NVs) and antimicrobial susceptibility testing (AST) phenotypes. The AMR phenotypes represented fluoroquinolones, tetracyclines, phenicols, and macrolides. Both models identified known and novel NVs associated (Bonferroni adjusted p < 0.05) with AMR. Fluoroquinolone resistance was associated with multiple NVs, including previously identified mutations in gyrA and parC. NVs in the 30S ribosomal protein 16S were associated with tetracycline resistance, whereas NVs in 5S rRNA, 23S rRNA, and 50S ribosomal proteins were associated with phenicol and macrolide resistance. For all antimicrobial classes, resistance was associated with NVs in genes coding for ABC transporters and other membrane proteins, tRNA-ligases, peptidases, and transposases, suggesting a NV-based multifactorial model of AMR in M. bovis. This study was the largest collection of North American M. bovis isolates used with a GWAS for the sole purpose of identifying novel and non-antimicrobial-target NVs associated with AMR.

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Macrolides, Azalides, and Ketolides

Prescott,

Baptiste

2024

Antimicrobial Therapy in Veterinary Medicine

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Genome-Wide Association Study Reveals Genetic Markers for Antimicrobial Resistance in Mycoplasma bovis

Abstract: Mycoplasma bovis is a leading cause of pneumonia but also causes other clinical signs in cattle. Since no effective vaccine is available, current M. bovis outbreak treatment relies primarily on the use of antimicrobials.

Cited by 30 publications

References 51 publications

Randomized field trial comparing the efficacy of florfenicol and oxytetracycline in a natural outbreak of calf pneumonia using lung reaeration as a cure criterion

Randomized field trial comparing the efficacy of florfenicol and oxytetracycline in a natural outbreak of calf pneumonia using lung reaeration as a cure criterion

Genome-Wide Association Study of Nucleotide Variants Associated with Resistance to Nine Antimicrobials in Mycoplasma bovis

Macrolides, Azalides, and Ketolides

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