Uropathogenic Escherichia coli Modulates Immune Responses and Its Curli Fimbriae Interact with the Antimicrobial Peptide LL-37

PLoS Pathogens

Matthew R. Chapman¹  Annelie Brauner²  Ylva Kai-Larsen²  Kjell-Olof Hedlund³  Petra Lüthje³  Milan Chromek³  Lavinia Kádas³  Xiaoda Wang⁴  Åsa Holm⁴  Birgitta Agerberth⁴  Stefan H. Jacobson⁵  Ute Römling⁶  Verena Peters⁷  Jan Johansson⁸ 

[1] Department of Anatomy, Physiology and Biochemistry, SLU, The Biomedical Centre, Uppsala, Sweden;Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden;Department of Microbiology, Tumor and Cell Biology, Stockholm, Sweden;Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America;Department of Nephrology, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden;Department of Pediatrics, CLINTEC, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden;Swedish Institute for Infectious Disease Control, Solna, Sweden

关键词: Cellulose;    Bacterial biofilms;    Epithelial cells;    Bacterial pathogens;    Pili;    fimbriae;    Urinary tract infections;    Escherichia coli infections;    Urine;   

DOI  :  10.1371/journal.ppat.1001010

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY