Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, China.
Antimicrob Agents Chemother. 2019 Sep 23;63(10). doi: 10.1128/AAC.00694-19. Print 2019 Oct.
is an important Gram-negative pathogen in hospital-related infections. However, treatment options for infections have become limited due to multidrug resistance. Bacterial virulence is often associated with capsule genes found in the K locus, many of which are essential for biosynthesis of the bacterial envelope. However, the roles of other genes in the K locus remain largely unknown. From an evolution experiment, we obtained an isolate of the virulent and multidrug-resistant strain MDR-ZJ06, called MDR-ZJ06, which has an insertion by the IS transposon in (encoding UDP--acetylglucosamine C-6 dehydrogenase), a gene found in the K locus. The isolate showed an increased resistance toward tigecycline, whereas the MIC decreased in the case of carbapenems, cephalosporins, colistin, and minocycline. By using knockout and complementation experiments, we demonstrated that is important for the synthesis of lipooligosaccharide and capsular polysaccharide and that disruption of the gene affects the morphology, drug susceptibility, and virulence of the pathogen.
是一种重要的与医院相关的革兰氏阴性病原体。然而，由于耐多药现象，感染的治疗选择变得有限。细菌的毒力通常与荚膜基因有关，这些基因存在于 K 基因座中，其中许多基因对细菌包膜的生物合成至关重要。然而，K 基因座中其他基因的作用在很大程度上仍然未知。通过进化实验，我们获得了一种毒力强且耐多药的 分离株 MDR-ZJ06，称为 MDR-ZJ06，其在 （编码 UDP--乙酰葡萄糖胺 C-6 脱氢酶）中插入了 IS 转座子，该基因存在于 K 基因座中。该分离株对替加环素的耐药性增加，而碳青霉烯类、头孢菌素类、多粘菌素和米诺环素的 MIC 降低。通过敲除和互补实验，我们证明了 对于脂寡糖和荚膜多糖的合成很重要，并且该基因的破坏会影响病原体的形态、药物敏感性和毒力。
