Dual Role of gnaA in Antibiotic Resistance and Virulence in Acinetobacter baumannii
Dual Role of gnaA in Antibiotic Resistance and Virulence in Acinetobacter baumannii
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gnaA 在鲍曼不动杆菌抗生素耐药性和毒力中的双重作用
DOI：
10.1128/aac.00694-19
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发表时间：
2019-10-01
影响因子：
4.9
通讯作者：
Hua, Xiaoting
中科院分区：
文献类型：
--
作者：
Xu, Qingye;Chen, Tao;Hua, Xiaoting
鲍曼不动杆菌是医院相关感染中重要的革兰氏阴性病原体。然而，由于多重耐药性，鲍曼不动杆菌感染的治疗选择已变得有限。细菌毒力通常与 K 基因座中发现的荚膜基因有关，其中许多基因对于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仍然很大程度上未知。摘要 鲍曼不动杆菌是医院相关感染中重要的革兰氏阴性病原体。然而，由于多重耐药性，鲍曼不动杆菌感染的治疗选择已变得有限。细菌毒力通常与 K 基因座中发现的荚膜基因有关，其中许多基因对于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仍然很大程度上未知。通过体外进化实验，我们获得了毒力和多重耐药鲍曼不动杆菌菌株 MDR-ZJ06 的分离株，称为 MDR-ZJ06M，该菌株在 gnaA（编码 UDP-N-乙酰氨基葡萄糖 C-6 脱氢酶）（K 基因座中发现的基因）中插入了 ISAba16 转座子。该分离株对替加环素的耐药性增加，而对碳青霉烯类、头孢菌素、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 gnaA 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。
Acinetobacter baumannii is an important Gram-negative pathogen in hospital-related infections. However, treatment options for A. baumannii 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. ABSTRACT Acinetobacter baumannii is an important Gram-negative pathogen in hospital-related infections. However, treatment options for A. baumannii 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 in vitro evolution experiment, we obtained an isolate of the virulent and multidrug-resistant A. baumannii strain MDR-ZJ06, called MDR-ZJ06M, which has an insertion by the ISAba16 transposon in gnaA (encoding UDP-N-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 gnaA 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.