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

• Published in: mBio Vol. 11; no. 1
• Main Authors: Ricci, Vito, Zhang, Dexian, Teale, Christopher, Piddock, Laura J V
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 28-01-2020
• Subjects: Anti-Bacterial Agents - pharmacology; Colistin - pharmacology; Epitopes - immunology; Genome, Bacterial; Humans; lipopolysaccharide; LPS; Microbial Sensitivity Tests; Mutation; O Antigens - immunology; Salmonella enterica - drug effects; Salmonella enterica - genetics; Salmonella enterica - immunology; Salmonella Enteritidis; Salmonella Infections - drug therapy; Salmonella Infections - immunology; Salmonella Infections - microbiology; Serogroup; Therapeutics and Prevention; Whole Genome Sequencing; lipopolysaccharide; whole-genome sequencing; LPS; Salmonella Enteritidis
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.02831-19

Group D and group B
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
governs the levels of colistin susceptibility. Substitution of the
gene in a group B
with the
genes from a group D
conferred a decrease in susceptibility to colistin. The presence of dideoxyhexose, abequose, and the deoxymannose, tyvelose, differentiate the
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
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
Some serovars of
, 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
serovar,
serovar Enteritidis. Here, we show that the O-antigen epitope in group D
governs the levels of colistin susceptibility. Using whole-genome sequencing, we also revealed that increased colistin susceptibility in a group D
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
.