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

Abstract

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.

Benchmarking AI-based plasmid annotation tools for antibiotic resistance genes mining from metagenome of the Virilla River, Costa Rica

“…These results can indicate the possibility of our findings regarding similar resistance genes to be integrated into chromosomes of the metagenome, explaining their absence in the plasmidomes. This hypothesis is supported by other genomic studies where the ARGs related to fluoroquinolone and tetracycline resistance are associated with the bacterial chromosome [33], [34].…”

<strong></strong>Effect of Erythromycin Residuals in Food on the Development of Resistance in <em>Streptococcus pneumoniae</em>: An <em>In Vivo</em> Study in <em>Galleria mellonella</em>

“…L1 serves as a ribosomal protein to bind rRNA and as a translational repressor binding its mRNA [63]. Studies in Mycoplasma bovis and Stenotrophomonas maltophilia have found that mutations in both L1 and L4 proteins were independently associated with elevated macrolide MICs [64,65]. For example, a genome wide association study in Mycoplasma bovis identified nucleotide variants in L1 and L4 as independently associated with macrolide MICs [65].…”

Phenotypic and genetic insights into efflux pump mechanism in Mycoplasma anserisalpingitidis

“…The role of the genes of ABC efflux pumps in the mechanism of antibacterial resistance in mycoplasmas has been previously described ( Pereyre et al, 2002 ; Raherison et al, 2002 , 2005 ; Antunes et al, 2015 ; Chernova et al, 2016 ), in contrast to other families of transport proteins. Furthermore, nsSNPs have been reported in the ABC efflux gene encoding regions of M. bovis ( Waldner et al, 2022 ), M. pneumoniae ( Li et al, 2017 ), and Streptococcus pneumoniae ( Lupien et al, 2013 ), as well as in the RND pumps of other bacterial species such as Acinetobacter baumannii, Escherichia coli, Legionella pneumophila, Neisseria gonorrhoeae, Pseudomonas aeruginosa , and Salmonella enterica ( Zwama and Nishino, 2021 ). SNPs related to antibiotic resistance have also been described in the promoter regions of efflux pumps, specifically in N. gonorrhoeae and Staphylococcus aureus ( Kaatz et al, 1999 ; Unemo et al, 2019 ).…”

“…Multiple studies have been published that have identified mutations associated with antibiotic resistance in the coding regions ( Lupien et al, 2013 ; Zwama and Nishino, 2021 ; Waldner et al, 2022 ) or the promoters ( Kaatz et al, 1999 ; Unemo et al, 2019 ) of various efflux pump genes in other bacteria. In the mechanism of antibacterial resistance of mycoplasmas, despite the presence of other transport protein families, only the significance of ABC efflux pumps has been previously established ( Pereyre et al, 2002 ; Raherison et al, 2005 ; Antunes et al, 2015 ; Chernova et al, 2016 ).…”

“…In the mechanism of antibacterial resistance of mycoplasmas, despite the presence of other transport protein families, only the significance of ABC efflux pumps has been previously established ( Pereyre et al, 2002 ; Raherison et al, 2005 ; Antunes et al, 2015 ; Chernova et al, 2016 ). Non-synonymous single nucleotide polymorphisms (nsSNPs) within the regions encoding ABC efflux genes have also been reported in cases of Mycoplasma bovis ( Waldner et al, 2022 ) and Mycoplasma pneumoniae ( Li et al, 2017 ). The current state of knowledge is limited regarding the regulation of the gene expression—including of ABC efflux genes—in mycoplasmas, because of the reduced genome and low percentage of genes involved in translation and transcription in these bacteria ( Madeira and Gabriel, 2007 ).…”