Polyphosphate kinase 1 is a pathogenesis determinant in Campylobacter jejuni
Polyphosphate kinase 1 is a pathogenesis determinant in Campylobacter jejuni
复制标题
DOI：
10.1128/jb.01037-07
复制
发表时间：
2007-11-01
影响因子：
3.2
通讯作者：
Gaynor, Erin C.
中科院分区：
文献类型：
--
作者：
Candon, Heather L.;Allan, Brenda J.;Gaynor, Erin C.
空肠弯曲菌是发达国家细菌性胃肠炎的主要病因。尽管它的流行，相对较少的人知道C。空肠的确切发病机制，特别是与其他研究充分的肠道微生物，如大肠杆菌和沙门氏菌属相比。改变了C. jejuni严格反应突变体，以及严格反应、多聚磷酸盐（poly-P）和其他细菌毒力之间已知的相关性，使我们研究了poly-P在C.空肠应激存活和发病机制。全部测序C.空肠菌株具有保守的推定的多磷酸激酶I，预测其主要负责多聚-P的合成。我们在C. jejuni菌株81-176中，并发现Δ ppk 1以及Δ spoT严格响应突变体在所有生长阶段都表现出低水平的聚-P。相反，野生型C.空肠多聚P水平随着细菌从对数期过渡到稳定期而显著增加。表型分析表明，三角洲ppk 1突变体是有缺陷的生存在渗透压休克和低营养胁迫。然而，在其他细菌中与ppk 1缺失相关的某些表型（即，运动和氧化应激）在C.空肠Delta ppk 1突变体，其也显示出生物膜形成的意外增加。梭空肠Delta ppk 1突变体在组织培养感染模型中也存在上皮内细胞存活的毒力相关表型缺陷，并表现出显著的剂量依赖性鸡定植缺陷。这些结果表明，聚磷的利用和积累对C。空肠发病机制，并影响其适应特定应力和严格性的能力。此外，我们的研究表明，聚P可能在C中发挥类似和独特的作用。jejuni的作用相比，其在其他细菌中的作用，聚磷代谢与严格的反应机制，在C。空肠。
Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, relatively little is known about C. jejuni's precise pathogenesis mechanisms, particularly in comparison to other well-studied enteric organisms such as Escherichia coli and Salmonella spp. Altered expression of phosphate genes in a C. jejuni stringent response mutant, together with known correlations between the stringent response, polyphosphate (poly-P), and virulence in other bacteria, led us to investigate the role of poly-P in C. jejuni stress survival and pathogenesis. All sequenced C. jejuni strains harbor a conserved putative polyphosphate kinase I predicted to be principally responsible for poly-P synthesis. We generated a targeted ppk1 deletion mutant (Delta ppk1) in C. jejuni strain 81-176 and found that Delta ppk1, as well as the Delta spoT stringent response mutant, exhibited low levels of poly-P at all growth stages. In contrast, wild-type C. jejuni poly-P levels increased significantly as the bacteria transitioned from log to stationary phase. Phenotypic analyses revealed that the Delta ppk1 mutant was defective for survival during osmotic shock and low-nutrient stress. However, certain phenotypes associated with ppk1 deletion in other bacteria (i.e., motility and oxidative stress) were unaffected in the C. jejuni Delta ppk1 mutant, which also displayed an unexpected increase in biofilm formation. The C. jejuni Delta ppk1 mutant was also defective for the virulence-associated phenotype of intraepithelial cell survival in a tissue culture infection model and exhibited a striking, dose-dependent chick colonization defect. These results indicate that poly-P utilization and accumulation contribute significantly to C. jejuni pathogenesis and affect its ability to adapt to specific stresses and stringencies. Furthermore, our study demonstrates that poly-P likely plays both similar and unique roles in C. jejuni compared to its roles in other bacteria and that poly-P metabolism is linked to stringent response mechanisms in C. jejuni.