Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37.
Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37.
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DOI：
10.1371/journal.ppat.1001010
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发表时间：
2010-07-22
期刊：
影响因子：
6.7
通讯作者：
Brauner A
中科院分区：
文献类型：
--
作者：
Kai-Larsen Y;Lüthje P;Chromek M;Peters V;Wang X;Holm A;Kádas L;Hedlund KO;Johansson J;Chapman MR;Jacobson SH;Römling U;Agerberth B;Brauner A
多细胞群落或生物膜中的细菌生长提供了许多优于单细胞生长的潜在优势，包括对抗菌因子的抗性。在这里，我们描述的生物膜促进组件卷曲菌毛和纤维素的尿路致病性大肠杆菌之间的相互作用。大肠杆菌和尿路中的内源性抗菌防御。我们还证明了这种相互作用对尿路感染发病机制的影响。我们的研究结果表明，curli和纤维素表现出差异和互补的功能。这两种生物膜成分均由高比例的临床E.大肠杆菌分离株。Curli促进了对上皮细胞的粘附和对人类抗菌肽LL-37的抗性，但也增加了促炎细胞因子IL-8的诱导。另一方面，纤维素的产生减少了免疫诱导，因此延迟了细菌从肾脏中的清除。有趣的是，LL-37通过阻止主要卷曲亚基CsgA的聚合来抑制卷曲形成。因此，即使是相对低浓度的LL-37也能在体外抑制卷曲介导的生物膜形成。综上所述，我们的数据表明，生物膜成分参与了尿路感染的发病机制，由E。大肠杆菌，并可以是局部免疫防御机制的目标。大多数尿路感染是由尿路致病性大肠杆菌引起的。杆菌在非生物表面上，这些细菌能够形成生物膜，保护它们免受各种不利环境条件的影响。在这项研究中，我们试图调查是否两个E。大肠杆菌生物膜组分、卷曲菌毛和纤维素提供了类似的针对泌尿道先天免疫防御机制的保护。我们特别强调了与人抗菌肽LL-37的相互作用，LL-37在预防尿路致病性E.杆菌我们证明curli表达通过在到达细菌细胞膜之前结合肽并表现出其杀菌活性来特异性地降低细菌对LL-37的敏感性。更普遍的保护作用是由纤维素介导的，可能是通过隐藏细菌的免疫原性表面结构。除了提供保护外，curli也是免疫系统的目标。在LL-37的存在下抑制新卷曲纤维的形成。此外，卷曲的细菌比它们的非卷曲的对应物显示更高的免疫原性。另一方面，纤维素的表达似乎会损害最初的宿主定植。总之，我们的研究结果证明了细菌毒力因子和宿主免疫防御之间紧密相互作用的一个例子。
Bacterial growth in multicellular communities, or biofilms, offers many potential advantages over single-cell growth, including resistance to antimicrobial factors. Here we describe the interaction between the biofilm-promoting components curli fimbriae and cellulose of uropathogenic E. coli and the endogenous antimicrobial defense in the urinary tract. We also demonstrate the impact of this interplay on the pathogenesis of urinary tract infections. Our results suggest that curli and cellulose exhibit differential and complementary functions. Both of these biofilm components were expressed by a high proportion of clinical E. coli isolates. Curli promoted adherence to epithelial cells and resistance against the human antimicrobial peptide LL-37, but also increased the induction of the proinflammatory cytokine IL-8. Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys. Interestingly, LL-37 inhibited curli formation by preventing the polymerization of the major curli subunit, CsgA. Thus, even relatively low concentrations of LL-37 inhibited curli-mediated biofilm formation in vitro. Taken together, our data demonstrate that biofilm components are involved in the pathogenesis of urinary tract infections by E. coli and can be a target of local immune defense mechanisms. Most infections of the urinary tract are caused by uropathogenic E. coli. On abiotic surfaces, these bacteria are able to form biofilms, which protect them from various adverse environmental conditions. In this study, we sought to investigate whether two E. coli biofilm components, curli fimbriae and cellulose, provide a similar protection against innate immune defense mechanisms of the urinary tract. We put special emphasis on the interaction with the human antimicrobial peptide LL-37, which plays a crucial role in the protection against uropathogenic E. coli. We demonstrate that curli expression specifically reduces bacterial sensitivity to LL-37 by binding the peptide before reaching the bacterial cell membrane and exhibiting its bactericidal activity. A more general protection is mediated by cellulose, possibly by hiding immunogenic surface structures of the bacterium. In addition to providing protection, curli are also targeted by the immune system. The formation of new curli fibers is inhibited in the presence of LL-37. Moreover, curliated bacteria show higher immunogenicity than their non-curliated counterparts. Cellulose expression, on the other hand, appears to impair initial host colonization. In conclusion, our findings demonstrate an example of the tight interplay between bacterial virulence factors and the host immune defense.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
5.6
作者：
Collinson, SK;Parker, JMR;Kay, WW
通讯作者：
Kay, WW
影响因子：
82.9
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
通讯作者：
Brauner, Annelie
影响因子：
3.6
作者：
Frendéus, B;Wachtler, C;Svanborg, C
通讯作者：
Svanborg, C
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL