Full Virulence of Pseudomonas aeruginosa Requires OprF
Full Virulence of Pseudomonas aeruginosa Requires OprF
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DOI：
10.1128/iai.00850-10
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发表时间：
2011-03-01
影响因子：
3.1
通讯作者：
Chevalier, Sylvie
中科院分区：
文献类型：
--
作者：
Fito-Boncompte, Laurene;Chapalain, Annelise;Chevalier, Sylvie
OprF是铜绿假单胞菌的一种常见的外膜孔蛋白，是一种众所周知的人类机会致病菌，与严重的医院获得性脓毒症和囊性纤维化患者的慢性肺部感染有关。基于对一株野生型铜绿假单胞菌、其等基因oprF突变株和一株oprF互补株的比较研究，多表型方法表明OprF是铜绿假单胞菌毒力所必需的。缺乏oprF导致与动物细胞的粘附性受损，通过III型分泌系统(T3SS)分泌ExoT和ExOS毒素，以及产生依赖群体感应的毒力因子绿青素、弹性蛋白酶、凝集素PA-1L和外毒素A。因此，在oprF突变体中，信号分子N-(3-氧代十二烷酰)-L-高丝氨酸内酯和N-丁酰基-L-高丝氨酸内酯的产生分别减少和延迟。假单胞菌的喹诺酮信号(PQs)产生减少，其前体4-羟基-2-庚基喹啉(HHQ)在细胞内积累。综上所述，这些结果表明OprF参与了铜绿假单胞菌的毒力，至少部分是通过调节群体感应网络。这是第一个显示OprF、PQS合成、T3SS和毒力因子产生之间联系的研究，为毒力表达提供了新的见解。
OprF is a general outer membrane porin of Pseudomonas aeruginosa, a well-known human opportunistic pathogen associated with severe hospital-acquired sepsis and chronic lung infections of cystic fibrosis patients. A multiphenotypic approach, based on the comparative study of a wild-type strain of P. aeruginosa, its isogenic oprF mutant, and an oprF-complemented strain, showed that OprF is required for P. aeruginosa virulence. The absence of OprF results in impaired adhesion to animal cells, secretion of ExoT and ExoS toxins through the type III secretion system (T3SS), and production of the quorum-sensing-dependent virulence factors pyocyanin, elastase, lectin PA-1L, and exotoxin A. Accordingly, in the oprF mutant, production of the signal molecules N-(3-oxododecanoyl)-L-homoserine lactone and N-butanoyl-L-homoserine lactone was found to be reduced and delayed, respectively. Pseudomonas quinolone signal (PQS) production was decreased, while its precursor, 4-hydroxy-2-heptylquinoline (HHQ), accumulated in the cells. Taken together, these results show the involvement of OprF in P. aeruginosa virulence, at least partly through modulation of the quorum-sensing network. This is the first study showing a link between OprF, PQS synthesis, T3SS, and virulence factor production, providing novel insights into virulence expression.