The Prevalence and the Underlying Mechanisms of Fosfomycin Resistance of Escherichia coli and Salmonella spp. Among Cattle in Japan

To investigate fosfomycin resistance rates in cattle across Japan, we carried out susceptibility tests. To identify the genes contributing to fosfomycin resistance, we performed whole-genome sequencing on the fosfomycin-resistant strains. <i>Escherichia coli</i> were sampled from healthy cattle (<i>n</i> = 292, combined total from 2017, 2020, 2021, and 2022) and diseased cattle (<i>n</i> = 73, from 2021 to 2022). <i>Salmonella</i> spp. were obtained from diseased cattle (<i>n</i> = 74 from 2021 to 2022). These samples originated from different and non-duplicated farms. The MICs to fosfomycin were measured using an agar dilution method with a breakpoint of 256 μg/mL. We conducted whole-genome sequencing with a MiSeq, followed by in silico analysis of the acquired draft genomes. The resistance rates were 0.3% (95% CI [0-1.9%]), 6.8% (95% CI [2.3-15.3%]), and 1.4% (95% CI [0-7.3%]). The <i>FosA3</i> gene was detected in five out of six fosfomycin-resistant <i>E. coli</i> strains and one <i>Salmonella</i> spp. strain. The fosfomycin-resistant <i>Salmonella</i> spp. strain also has a <i>fosA7</i> gene. One <i>E. coli</i> strain showed resistance to fosfomycin without having the <i>fosA3</i> gene, and with the mutations of <i>glpT</i>, <i>uhpT</i>, <i>uhpT</i> and <i>ptsI</i>, and with the existence of efflux pumps. The nationwide scale of resistance rates to fosfomycin in <i>E. coli</i> isolated from healthy and diseased cattle and that of <i>Salmonella</i> spp. from diseased cattle were revealed for the first time, and the resistance rates were low. In addition, genes linked to the mechanism of fosfomycin resistance were identified.