The O-Antigen Epitope Governs Susceptibility to Colistin in Salmonella enterica

• Main Authors: Vito Ricci, Dexian Zhang, Christopher Teale, Laura J. V. Piddock
• Format: Article
• Language: English
• Published: American Society for Microbiology 2020-01-01
• Series: mBio
• Subjects: whole-genome sequencing; lps; salmonella enteritidis; lipopolysaccharide
• Online Access: https://doi.org/10.1128/mBio.02831-19

Some serovars of Salmonella, namely, those belonging to group D, appear to show a degree of intrinsic resistance to colistin. This observed intrinsic colistin resistance is of concern since this last-resort drug might no longer be effective for treating severe human infections with the most common Salmonella serovar, Salmonella enterica serovar Enteritidis. Here, we show that the O-antigen epitope in group D Salmonella governs the levels of colistin susceptibility. Using whole-genome sequencing, we also revealed that increased colistin susceptibility in a group D Salmonella veterinary isolate was due to a defect in the O-antigen polymerase protein, Rfc. In summary, we show that two different mechanisms that influence the presence and composition of O antigens affect colistin susceptibility in Salmonella enterica.Group D and group B Salmonella enterica serovars differ in their susceptibility to colistin with the former frequently intrinsically resistant (MIC > 2 μg/ml); however, the mechanism has not been described. Here, we show that the O-antigen epitope in group D Salmonella governs the levels of colistin susceptibility. Substitution of the rfbJ gene in a group B Salmonella with the rfbSE genes from a group D Salmonella conferred a decrease in susceptibility to colistin. The presence of dideoxyhexose, abequose, and the deoxymannose, tyvelose, differentiate the Salmonella group B and group D O antigens, respectively. We hypothesize that the subtle difference between abequose and tyvelose hinders the colistin molecule from reaching its target. Whole-genome sequencing also revealed that increased colistin susceptibility in a group D Salmonella veterinary isolate was due to a defect in the O-antigen polymerase protein, Rfc. This study shows that two different mechanisms that influence the presence and composition of O antigens affect colistin susceptibility in Salmonella enterica.