Structural function of multidrug-resistant Salmonella carrying mcr-1 gene in colistin resistance

Colistin, also known as polymyxin E, is extensively used in veterinary and human medicine as a last line of defense against Gram-negative bacteria. Therefore, it is essential to monitor the development of resistance to this antibiotic to combat infections caused by multidrug-resistant bacteria. This study focuses on investigating the presence of the colistin resistance gene mcr-1 in Salmonella isolates. A total of 24 Salmonella spp. were identified and analyzed from 200 cattle fecal samples. Phenotypic disc diffusion and a MIC assay using various antimicrobial agents were performed and assessed using the VITEK2 compact system. The isolates were further examined through PCR targeting the invA and mcr-1 genes. Among the 24 isolates, two exhibited phenotypic resistance to colistin, while one isolate harbored the mcr-1 gene. Notably, 14 (58.33%) of the 24 Salmonella isolates showed multidrug resistance. Furthermore, in-silico functional studies were conducted to explore the genetic relationships and phenotypic correlations among these colistin-resistant isolates. Sequencing and phylogenetic analysis revealed a significant evolutionary association between the catalytic region of Neisseria meningitidis EptA and MCR proteins. Structural modeling indicated that MCR-1 has five essential transmembrane regions for its function in colistin resistance. Molecular docking interaction studies demonstrated distinct binding mechanisms between MCR-1 and EptA proteins. This study highlights the occurrence of mcr-1 carrying Salmonella in cattle from Bangladesh, underscoring the urgent need for robust AMR surveillance and stringent antibiotic use policies in agriculture to mitigate the spread of multidrug-resistant pathogens.