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 entericaIMPORTANCE 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.