Polymyxin Resistance in : Exploring Mutations and Genetic Determinants of Non-Human Isolates.

Until 2015, polymyxin resistance was primarily attributed to chromosomal mutations. However, with the first report of mobile colistin resistance () in commensal from food animals in China, the landscape has changed. To evaluate the presence of polymyxin resistance in spp., a drop screening test for colistin and polymyxin B was carried out on 1156 isolates of non-human origin (animals, food, and the environment), received in Brazil, between 2016 and 2021. Subsequently, 210 isolates with resistant results in the drop test were subjected to the gold-standard test (broth microdilution) for both colistin and polymyxin B. Whole-genome sequencing (WGS) of 102 resistant isolates was performed for a comprehensive analysis of associated genes. Surprisingly, none of the isolates resistant to colistin in the drop test harbored any of the variants ( to ). WGS identified that the most common mutations were found in (n= 22; T89S) and (n = 24; M15T, G73S, V74I, I83A, A111V). Other resistance determinants were also detected, such as the (')- gene in 72 isolates, while others carried beta-lactamase genes (, ). Additionally, genes associated with fluoroquinolone resistance (, , ) were detected in 11 isolates. Colistin and polymyxin B resistance were identified among from non-human sources, but not associated with the genes. Furthermore, the already-described mutations associated with polymyxin resistance were detected in only a small number of isolates, underscoring the need to explore and characterize unknown genes that contribute to resistance.