An Acinetobacter baumannii, Zinc-Regulated Peptidase Maintains Cell Wall Integrity during Immune-Mediated Nutrient Sequestration
An Acinetobacter baumannii, Zinc-Regulated Peptidase Maintains Cell Wall Integrity during Immune-Mediated Nutrient Sequestration
复制标题
DOI：
10.1016/j.celrep.2019.01.089
复制
发表时间：
2019-02-19
期刊：
影响因子：
8.8
通讯作者：
Skaar, Eric P.
中科院分区：
文献类型：
--
作者：
Lonergan, Zachery R.;Nairn, Brittany L.;Skaar, Eric P.
鲍曼不动杆菌是一种重要的医院病原体，能够引起伤口感染、肺炎和菌血症。在感染过程中，A.鲍曼不动杆菌必须获得锌以存活并定殖宿主。脊椎动物已经进化出一种机制，通过一种称为营养免疫的过程从入侵的病原体中隔离锌。在锌饥饿期间上调最多的基因之一编码我们命名为ZrlA的推定的细胞壁修饰酶。我们发现zrlA的失活减少了A.鲍曼不动杆菌在锌饥饿期间的生长。此外，该突变株显示细胞被膜通透性增加、膜屏障功能降低和异常肽聚糖胞肽丰度。这种改变的包膜增加了体外和A.鲍氏肺炎。这些结果确立了ZrlA作为A.鲍曼不动杆菌的发病机制，这可能是治疗发展的目标。
Acinetobacter baumannii is an important nosocomial pathogen capable of causing wound infections, pneumonia, and bacteremia. Duringinfection, A. baumannii must acquire Zn to survive and colonize the host. Vertebrates have evolved mechanisms to sequester Zn from invading pathogens by a process termed nutritional immunity. One of the most upregulated genes during Zn starvation encodes a putative cell wall- modifying enzyme which we named ZrlA. We found that inactivation of zrlA diminished growth of A. baumannii during Zn starvation. Additionally, this mutant strain displays increased cell envelope permeability, decreased membrane barrier function, and aberrant peptidoglycan muropeptide abundances. This altered envelope increases antibiotic efficacy both in vitro and in an animal model of A. baumannii pneumonia. These results establish ZrlA as a crucial link between nutrient metal uptake and cell envelope homeostasis during A. baumannii pathogenesis, which could be targeted for therapeutic development.