The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii.
The lytic transglycosylase MltB connects membrane homeostasis and in vivo fitness of Acinetobacter baumannii.
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DOI：
10.1111/mmi.14000
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发表时间：
2018-09
影响因子：
3.6
通讯作者：
Mobley HLT
中科院分区：
文献类型：
--
作者：
Crépin S;Ottosen EN;Peters K;Smith SN;Himpsl SD;Vollmer W;Mobley HLT
鲍曼不动杆菌已成为一种主要的医院病原体，感染包括呼吸道和血液在内的广泛解剖部位。除了多重耐药性之外，人们对鲍曼不动杆菌发病机制的分子基础知之甚少。为了更好地了解鲍曼不动杆菌的毒力，结合使用转座子测序（TraDIS）筛选和中性粒细胞减少小鼠菌血症模型来识别血流感染期间所需的全套适应基因。裂解性转糖基酶 MltB 被确定为关键的适应因子。 MltB 裂解肽聚糖的 MurNAc-GlcNAc 键，从而导致细胞壁重塑。在这里，我们证明 MltB 是连接压力抵抗、膜稳态、菌毛生物发生和体内健康的复杂网络的一部分。事实上，mltB 失活不仅损害对血清补体、阳离子抗菌肽和氧物种的抵抗力，而且改变细胞包膜完整性，激活包膜应激反应，大大减少细胞表面的菌毛数量，最后显着减少血流和呼吸道的定植。
Acinetobacter baumannii has emerged as a leading nosocomial pathogen, infecting a wide range of anatomic sites including the respiratory tract and the bloodstream. In addition to being multi‐drug resistant, little is known about the molecular basis of A. baumannii pathogenesis. To better understand A. baumannii virulence, a combination of a transposon‐sequencing (TraDIS) screen and the neutropenic mouse model of bacteremia was used to identify the full set of fitness genes required during bloodstream infection. The lytic transglycosylase MltB was identified as a critical fitness factor. MltB cleaves the MurNAc‐GlcNAc bond of peptidoglycan, which leads to cell wall remodeling. Here we show that MltB is part of a complex network connecting resistance to stresses, membrane homeostasis, biogenesis of pili and in vivo fitness. Indeed, inactivation of mltB not only impaired resistance to serum complement, cationic antimicrobial peptides and oxygen species, but also altered the cell envelope integrity, activated the envelope stress response, drastically reduced the number of pili at the cell surface and finally, significantly decreased colonization of both the bloodstream and the respiratory tract.
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DOI：
10.1073/pnas.1611594113
发表时间：
2016-10-11
影响因子：
11.1
作者：
Boll, Joseph M.;Crofts, Alexander A.;Trent, M. Stephen
通讯作者：
Trent, M. Stephen
影响因子：
3.1
作者：
Crepin, Sebastien;Houle, Sebastien;Dozois, Charles M.
通讯作者：
Dozois, Charles M.
影响因子：
3.1
作者：
Gaddy, Jennifer A.;Arivett, Brock A.;Actis, Luis A.
通讯作者：
Actis, Luis A.
影响因子：
11.8
作者：
Fagon, JY;Chastre, J;Gibert, C
通讯作者：
Gibert, C
影响因子：
6.4
作者：
Gebhardt MJ;Gallagher LA;Jacobson RK;Usacheva EA;Peterson LR;Zurawski DV;Shuman HA
通讯作者：
Shuman HA