Whole genome sequence analysis reveals the broad distribution of the RtxA type 1 secretion system and four novel putative type 1 secretion systems throughout the Legionella genus

Whole genome sequence analysis reveals the broad distribution of the RtxA type 1 secretion system and four novel putative type 1 secretion systems throughout the Legionella genus
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DOI:
10.1371/journal.pone.0223033
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发表时间:
2020-01-14
期刊:
影响因子:
3.7
通讯作者:
Pruden, Amy J.
Pruden, Amy J.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Brown, Connor L.;Garner, Emily;Pruden, Amy J.

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1 型分泌系统 (T1SS) 广泛分布在细菌中,并在细菌细胞膜上转运具有多种功能的效应器。嗜肺军团菌是最常与军团病相关的物种,在 lssXY-ZABD 基因座编码 T1SS,负责毒力因子 RtxA 的分泌。许多研究未能在非嗜肺军团菌中检测到lssD(编码RtxA T1SS膜融合蛋白的基因),这导致人们假设该系统是嗜肺军团菌独有的毒力因子。在这里,我们在一种新的牛磺酸军团菌菌株中发现了 RtxA 及其相关的 T1SS,这让我们怀疑这个系统是否可能比之前想象的更广泛。通过对公开数据的生物信息学分析,我们分类并确定了四种 T1SS(包括 RtxA T1SS)和四种新型 T1SS 在不同军团菌中的分布。新型军团菌 T1SS 军团菌重复蛋白分泌系统的 ABC 转运蛋白与不同 T1SS 家族的转运蛋白具有结构相似性,包括铜绿假单胞菌中的碱性蛋白酶 T1SS。军团菌细菌素 (1-3) 分泌系统 T1SS 是新型假定的细菌素转运 T1SS,因为它们的 ABC 转运蛋白在其 N 末端区域包含 C-39 肽酶结构域,LB2SS 和 LB3SS 可能构成腈水合酶前导肽转运 T1SS。 LB1SS 与大肠杆菌中的大肠菌素 V T1SS 关系更密切。共 45 种军团菌。通过检查整个基因组,19 个(42%)被确定具有 lssB 和 lssD 同源物。在这 19 种病原体中,只有 7 种(37%)是已知病原体。拥有 RtxA T1SS 的疾病相关和非疾病相关物种的比例没有差异 (p = 0.4),这与目前关于 RtxA T1SS 的共识相反。这些结果对 RtxA 及其 T1SS 作为单一毒力因子的性质提出了质疑。未来的研究应该调查 RtxA 与毒力关联的机制解释。
Type 1 secretion systems (T1SSs) are broadly distributed among bacteria and translocate effectors with diverse function across the bacterial cell membrane. Legionella pneumophila, the species most commonly associated with Legionellosis, encodes a T1SS at the lssXY-ZABD locus which is responsible for the secretion of the virulence factor RtxA. Many investigations have failed to detect lssD, the gene encoding the membrane fusion protein of the RtxA T1SS, in non-pneumophila Legionella, which has led to the assumption that this system is a virulence factor exclusively possessed by L. pneumophila. Here we discovered RtxA and its associated T1SS in a novel Legionella taurinensis strain, leading us to question whether this system may be more widespread than previously thought. Through a bioinformatic analysis of publicly available data, we classified and determined the distribution of four T1SSs including the RtxA T1SS and four novel T1SSs among diverse Legionella spp. The ABC transporter of the novel Legionella T1SS Legionella repeat protein secretion system shares structural similarity to those of diverse T1SS families, including the alkaline protease T1SS in Pseudomonas aeruginosa. The Legionella bacteriocin (1-3) secretion systems T1SSs are novel putative bacteriocin transporting T1SSs as their ABC transporters include C-39 peptidase domains in their N-terminal regions, with LB2SS and LB3SS likely constituting a nitrile hydratase leader peptide transport T1SSs. The LB1SS is more closely related to the colicin V T1SS in Escherichia coli. Of 45 Legionella spp. whole genomes examined, 19 (42%) were determined to possess lssB and lssD homologs. Of these 19, only 7 (37%) are known pathogens. There was no difference in the proportions of disease associated and non-disease associated species that possessed the RtxA T1SS (p = 0.4), contrary to the current consensus regarding the RtxA T1SS. These results draw into question the nature of RtxA and its T1SS as a singular virulence factor. Future studies should investigate mechanistic explanations for the association of RtxA with virulence.