Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Clinical Pharmacy Undergraduate Program, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Infect Dis. 2020 Aug 4;222(5):871-879. doi: 10.1093/infdis/jiaa262.
A thorough understanding of Acinetobacter baumannii pathogenicity is the key to identifying novel drug targets. In the current study, we characterize the γ-glutamyltransferase enzyme (GGT) as a novel virulence factor. A GGT assay showed that the enzyme is secreted via the type II secretion system and results in higher extracellular activity for the hypervirulent AB5075 than the laboratory-adapted strain American Type Culture Collection 17978. Enzyme-linked immunosorbent assay revealed that the former secretes larger amounts of GGT, and a rifampicin messenger RNA stability study showed that one reason for this could be the longer AB5075 ggt transcript half-life. Infection models confirmed that GGT is required for the virulence of A. baumannii. Finally, we show that clinical isolates with significantly higher extracellular GGT activity resulted in more severe infections, and assay of immune response and tissue damage markers confirm this correlation. The current findings establish for the first time the role of the GGT in the pathogenicity of A. baumannii.
深入了解鲍曼不动杆菌的致病性是确定新药物靶点的关键。在本研究中，我们将 γ-谷氨酰转移酶（GGT）鉴定为一种新的毒力因子。GGT 测定表明，该酶通过 II 型分泌系统分泌，并使高毒力 AB5075 株的细胞外活性高于实验室适应株美国模式培养物集存库 17978 株。酶联免疫吸附试验显示前者分泌更多的 GGT，利福平 mRNA 稳定性研究表明，其原因之一可能是 AB5075 株 ggt 转录本半衰期更长。感染模型证实 GGT 是鲍曼不动杆菌毒力所必需的。最后，我们表明具有更高细胞外 GGT 活性的临床分离株可导致更严重的感染，并且对免疫反应和组织损伤标志物的检测证实了这种相关性。目前的研究结果首次确立了 GGT 在鲍曼不动杆菌致病性中的作用。
