InvL, an Invasin-Like Adhesin, Is a Type II Secretion System Substrate Required for Acinetobacter baumannii Uropathogenesis.
InvL, an Invasin-Like Adhesin, Is a Type II Secretion System Substrate Required for Acinetobacter baumannii Uropathogenesis.
复制标题
DOI：
10.1128/mbio.00258-22
复制
发表时间：
2022-06-28
期刊：
影响因子：
6.4
通讯作者：
Feldman, Mario F.
中科院分区：
文献类型：
--
作者：
Jackson-Litteken, Clay D.;Di Venanzio, Gisela;Nguyen-Hung Le;Scott, Nichollas E.;Djahanschiri, Bardya;Distel, Jesus S.;Pardue, Evan J.;Ebersberger, Ingo;Feldman, Mario F.
关键词：
鲍曼不动杆菌是一种日益受到关注的机会致病菌，因为其分离株通常具有多重耐药性。虽然鲍曼不动杆菌最常与肺部感染有关，但相当大比例的临床分离株来自泌尿系统，这凸显了其致泌尿系统感染的潜力。常用的不动杆菌模式菌株的II型分泌系统（T2SS）在多种动物模型中对毒力很重要，但T2SS在尿路感染（UTI）中的潜在作用仍然未知。在此，我们使用了一种导管相关尿路感染（CAUTI）模型来证明一种现代泌尿系统分离株UPAB1需要T2SS才能具有完全的毒力。通过蛋白质组学筛选来鉴定假定的UPAB1 T2SS效应子，发现了一种未表征的脂蛋白，其结构与紧密素 - 侵袭素家族相似，紧密素 - 侵袭素家族是几种细菌致病所需的V型分泌系统（T5SS）黏附素。这种蛋白质被命名为InvL，它缺乏与T5SS相关的β - 桶状结构域，但经证实其表面定位和分泌都需要T2SS。这使得InvL成为第一个被鉴定出的属于紧密素 - 侵袭素家族的T2SS效应子。InvL被证实是一种黏附素，因为该蛋白质在体外能与细胞外基质成分结合，并介导对泌尿系统细胞系的黏附。此外，invL突变体在CAUTI模型中的毒力减弱，表明它在鲍曼不动杆菌致泌尿系统疾病中起作用。最后，生物信息学分析显示，InvL存在于几乎所有属于国际克隆2的临床分离株中，国际克隆2是一个具有重要临床意义的谱系。总之，我们得出结论，T2SS底物InvL是鲍曼不动杆菌致泌尿系统疾病所必需的一种黏附素。
Acinetobacter baumannii is an opportunistic pathogen of growing concern, as isolates are commonly multidrug resistant. While A. baumannii is most frequently associated with pulmonary infections, a significant proportion of clinical isolates come from urinary sources, highlighting its uropathogenic potential. The type II secretion system (T2SS) of commonly used model Acinetobacter strains is important for virulence in various animal models, but the potential role of the T2SS in urinary tract infection (UTI) remains unknown. Here, we used a catheter-associated UTI (CAUTI) model to demonstrate that a modern urinary isolate, UPAB1, requires the T2SS for full virulence. A proteomic screen to identify putative UPAB1 T2SS effectors revealed an uncharacterized lipoprotein with structural similarity to the intimin-invasin family, which serve as type V secretion system (T5SS) adhesins required for the pathogenesis of several bacteria. This protein, designated InvL, lacked the β-barrel domain associated with T5SSs but was confirmed to require the T2SS for both surface localization and secretion. This makes InvL the first identified T2SS effector belonging to the intimin-invasin family. InvL was confirmed to be an adhesin, as the protein bound to extracellular matrix components and mediated adhesion to urinary tract cell lines in vitro. Additionally, the invL mutant was attenuated in the CAUTI model, indicating a role in Acinetobacter uropathogenesis. Finally, bioinformatic analyses revealed that InvL is present in nearly all clinical isolates belonging to international clone 2, a lineage of significant clinical importance. In all, we conclude that the T2SS substrate InvL is an adhesin required for A. baumannii uropathogenesis.
登录
查看更多内容
影响因子：
4.5
作者：
Crua Asensio N;Macho Rendón J;Torrent Burgas M
通讯作者：
Torrent Burgas M
抗生素抗生素抗生素的作用在尿路感染的发病机理中以及其使用噬菌体治疗的治疗潜力。
DOI：
10.3390/antibiotics10030281
发表时间：
2021-03-09
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
--
作者：
Bagińska N;Cieślik M;Górski A;Jończyk-Matysiak E
通讯作者：
Jończyk-Matysiak E
DOI：
10.1073/pnas.95.23.13658
发表时间：
1998-11-10
影响因子：
11.1
作者：
Alrutz, MA;Isberg, RR
通讯作者：
Isberg, RR
影响因子：
4.1
作者：
An, Zhiyuan;Huang, Xiaoxi;Ding, Wenyi
通讯作者：
Ding, Wenyi
影响因子：
11.4
作者：
DENFERT, C;RYTER, A;PUGSLEY, AP
通讯作者：
PUGSLEY, AP