Identification of non-dot/icm suppressors of the Legionella pneumophila DeltadotL lethality phenotype.
Identification of non-dot/icm suppressors of the Legionella pneumophila DeltadotL lethality phenotype.
复制标题
嗜肺军团菌 DeltadotL 致死表型的非点/icm 抑制因子的鉴定。
DOI：
10.1128/jb.00937-06
复制
发表时间：
2006
影响因子：
3.2
通讯作者：
Vogel,JosephP
中科院分区：
文献类型：
--
作者：
Vincent,CarrD;Buscher,BenjaminA;Friedman,JonathanR;Williams,LeeAnne;Bardill,Patrick;Vogel,JosephP
嗜肺军团菌是细菌性肺炎的病原体，通过避免快速靶向溶酶体而在吞噬细胞内存活。这种细菌利用由dot/icm基因编码的IVB型分泌系统在宿主细胞内复制。DotL是Dot/Icm分泌装置的关键组分，其功能为IV型偶联蛋白。与大多数dot/icm基因相反，它们在细菌培养基上生长，dotL是野生型L生存所必需的。嗜肺菌以前我们报道过，Δ dotL致死率可以通过其他dot/icm基因的突变通过Dot/icm复合物的失活来抑制。在这里，我们报告分离的非点/icm抑制这种表型。这些Δ dotL抑制子包括破坏L功能的插入。pneumophila同源物cpxR，djlA，lysS和两个新的开放阅读框架lpg 0742和lpg 1594，我们命名为ldsA和ldsB，用于ΔdotL抑制子的致死性。除了抑制Δ dotL致死性，在野生型菌株背景中这些基因的失活导致L中的一系列缺陷。嗜肺性毒力性状，包括细胞内生长，暗示这些因子在Dot/Icm复合物的适当功能中。与先前的数据显示px系统在调节几个dot/icm基因表达中的作用一致，pxR插入突变体产生了三种Dot/Icm蛋白DotA、IcmV和IcmW的降低水平。其余四个抑制因子不影响任何Dot/Icm蛋白的稳态水平，并且可能代表组装和/或激活Dot/Icm分泌复合物所必需的第一个鉴定的因子。
Legionella pneumophila, a causative agent of bacterial pneumonia, survives inside phagocytic cells by avoiding rapid targeting to the lysosome. This bacterium utilizes a type IVB secretion system, encoded by thedot/icmgenes, to replicate inside host cells. DotL, a critical component of the Dot/Icm secretion apparatus, functions as the type IV coupling protein. In contrast to mostdot/icmgenes, which are dispensable for growth on bacteriological media,dotLis required for the viability of wild-typeL. pneumophila. Previously we reported that ΔdotLlethality could be suppressed by inactivation of the Dot/Icm complex via mutations in otherdot/icmgenes. Here we report the isolation of non-dot/icmsuppressors of this phenotype. These ΔdotLsuppressors include insertions that disrupt the function of theL. pneumophilahomologs ofcpxR,djlA,lysS, and two novel open reading frames, lpg0742 and lpg1594, that we have namedldsAandldsBforlethality of ΔdotL suppressor. In addition to suppressing ΔdotLlethality, inactivation of these genes in a wild-type strain background causes a range of defects inL. pneumophilavirulence traits, including intracellular growth, implicating these factors in the proper function of the Dot/Icm complex. Consistent with previous data showing a role for thecpxsystem in regulating expression of severaldot/icmgenes, thecpxRinsertion mutant produced decreased levels of three Dot/Icm proteins, DotA, IcmV, and IcmW. The remaining four suppressors did not affect the steady-state levels of any Dot/Icm protein and are likely to represent the first identified factors necessary for assembly and/or activation of the Dot/Icm secretion complex.