The O-Antigen Epitope Governs Susceptibility to Colistin in Salmonella enterica.
The O-Antigen Epitope Governs Susceptibility to Colistin in Salmonella enterica.
复制标题
O 抗原表位控制肠道沙门氏菌对粘菌素的敏感性。
作者：
Ricci V
D组和B组沙门氏菌血清型对粘菌素的敏感性不同，前者通常具有内在耐药性（MIC > 2 μg/ml）;然而，其机制尚未描述。在这里，我们表明，O-抗原表位在组D沙门氏菌控制水平的粘菌素的敏感性。将B群沙门氏菌的thefbJ基因替换为D群沙门氏菌的thefbSE基因可降低对粘菌素的敏感性。双脱氧己糖、阿贝糖和脱氧甘露糖、泰维糖的存在分别区分了沙门氏菌属B群和D O群抗原。我们假设阿贝戈糖和泰维糖之间的细微差异阻碍了粘菌素分子到达其靶标。全基因组测序还显示，D组沙门氏菌兽医分离株中粘菌素敏感性增加是由于O-抗原聚合酶蛋白Rfc的缺陷。这项研究表明，两种不同的机制，影响的存在和组成的O抗原影响粘菌素的敏感性在沙门氏菌enterica.IMPORTANCEsome血清型ofSalmonella，即那些属于D组，似乎表现出一定程度的内在耐药性粘菌素。这种观察到的内在粘菌素耐药性令人担忧，因为这种最后手段的药物可能不再有效治疗最常见的沙门氏菌，肠道沙门氏菌肠道血清型的严重人类感染。在这里，我们表明，O-抗原表位在组D沙门氏菌控制水平的粘菌素的敏感性。使用全基因组测序，我们还发现，增加粘菌素的敏感性在一组D沙门氏菌兽医分离是由于在O-抗原聚合酶蛋白，Rfc的缺陷。总之，我们表明，两种不同的机制，影响的存在和组成的O抗原影响肠沙门氏菌的粘菌素的敏感性。
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 DSalmonellagoverns the levels of colistin susceptibility. Substitution of therfbJgene in a group BSalmonellawith therfbSEgenes from a group DSalmonellaconferred a decrease in susceptibility to colistin. The presence of dideoxyhexose, abequose, and the deoxymannose, tyvelose, differentiate theSalmonellagroup 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 DSalmonellaveterinary 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.IMPORTANCESome serovars ofSalmonella, 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 commonSalmonellaserovar, Salmonella enterica serovar Enteritidis. Here, we show that the O-antigen epitope in group DSalmonellagoverns the levels of colistin susceptibility. Using whole-genome sequencing, we also revealed that increased colistin susceptibility in a group DSalmonellaveterinary 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.