PDF(Pubmed)
Abstract：
Adherent and invasive Escherichia coli (AIEC) is a pathobiont that is involved in the onset and exacerbation of Crohn\'s disease. Although the inducible expression of virulence traits is a critical step for AIEC colonization in the host, the mechanism underlying AIEC colonization remains largely unclear. We here showed that the two-component signal transduction system CpxRA contributes to AIEC gut competitive colonization by activating type 1 fimbriae expression. CpxRA from AIEC strain LF82 functioned as a transcriptional regulator, as evidenced by our finding that an isogenic cpxRA mutant exhibits reduced expression of cpxP, a known regulon gene. Transcription levels of cpxP in LF82 increased in response to envelope stress, such as exposure to antimicrobials compromising the bacterial membrane, whereas the cpxRA mutant did not exhibit this response. Furthermore, we found that the cpxRA mutant exhibits less invasiveness into host cells than LF82, primarily due to reduced expression of the type 1 fimbriae. Finally, we found that the cpxRA mutant is impaired in gut competitive colonization in a mouse model. The colonization defects were reversed by the introduction of a plasmid encoding the cpxRA gene or expressing the type 1 fimbriae. Our findings indicate that modulating CpxRA activity could be a promising approach to regulating AIEC-involved Crohn\'s disease.
摘要：
粘附性和侵袭性大肠杆菌(AIEC)是一种与克罗恩病的发病和恶化有关的病原体。尽管毒力性状的诱导型表达是AIEC在宿主中定植的关键步骤，AIEC定殖的潜在机制仍不清楚.我们在这里表明，双组分信号转导系统CpxRA通过激活1型菌毛表达而有助于AIEC肠道竞争性定植。来自AIEC菌株LF82的CpxRA充当转录调节因子，正如我们的发现所证明的，一个等基因的cpxRA突变体表现出减少的cpxP的表达，一个已知的调节子基因.LF82中cpxP的转录水平响应于包膜胁迫而增加，例如暴露于损害细菌膜的抗微生物剂，而cpxRA突变体没有表现出这种反应。此外，我们发现cpxRA突变体对宿主细胞的侵袭性比LF82小，这主要是由于1型菌毛的表达减少。最后,我们发现cpxRA突变体在小鼠模型的肠道竞争性定植中受损。通过引入编码cpxRA基因或表达1型菌毛的质粒，可以逆转定殖缺陷。我们的发现表明，调节CpxRA活性可能是调节AIEC参与的克罗恩病的一种有希望的方法。
