Curli of Uropathogenic Escherichia coli Enhance Urinary Tract Colonization as a Fitness Factor

Abstract

Curli, a type of fimbriae widely distributed in uropathogenic Escherichia coli (UPEC), are involved in adhesion to human bladder cell surfaces and biofilm development. The role of UPEC curli was evaluated in a murine model of urinary tract infection. The aim of this study was to establish the role of curli in C57BL/6 mice transurethrally infected with curli-producing and non-curli-producing UPEC strains. We confirmed that curli enhanced UPEC colonization in the urinary tract, resulting in damage to both the bladder and kidney. Intranasal immunization with recombinant CsgA protein protected against colonization by curli-producing UPEC in the urinary tract. Quantification of cytokines from urinary tract organs showed increases in interleukin-6 and tumor necrosis factor (TNF) release in the kidneys 48 h postinfection with curli-producing UPEC. By contrast, mice infected with non-curli-producing UPEC showed the highest release of interleukin-6, -10, and -17A and TNF. Curli may obscure other fimbriae and LPS, preventing interactions with Toll-like receptors. When intranasal immunization with recombinant FimH and PapG proteins and subsequent infection with this strain were performed, cytokine quantification showed a decrease in the stimulation and release by the uroepithelium. Thus, curli are amyloid-like fimbriae that enhances colonization in the urinary tract and a possible fitness factor.

Antibiofilm and Antimicrobial Activities of Chloroindoles Against Uropathogenic Escherichia coli

“…Curli fimbriae are a type of amyloid fiber that facilitates surface adhesion, cell aggregation, and biofilm formation in the family Enterobacteriaceae ( Kikuchi et al, 2005 ). Curli formation is regulated by the csg DEFG and csg AB operons ( Chapman et al, 2002 ), and Curli plays an essential role in the colonization of the urinary tract, biofilm formation, and the persistence of UPEC post-interaction with antimicrobial peptides ( Luna-Pineda et al, 2019 ). Iron acquisition is essential for UPEC survival in iron-deficient environments like the urinary tract, and UPEC expresses siderophores (small-molecule iron-chelators that scavenge the ferric ion) such as enterobactin, which can outcompete transferrin (a mammalian iron carrier with a K d of ~10 −45 ) and enable UPEC survival in the urinary tract ( Goetz et al, 2002 ; O'Brien et al, 2016 ).…”

Distinct Characteristics of Escherichia coli Isolated from Patients with Urinary Tract Infections in a Medical Center at a Ten-Year Interval

“…Type 1 fimbrial adhesin FimH has a critical role not only in lower UTI pathogenesis but also in kidney infections by acting synergistically with PapGII [ 8 ]. Moreover, fimbriae [ 12 ], iron acquisition systems [ 13 ], iron-regulated gene homologue adhesin Iha [ 14 ], ferric aerobactin receptor IutA [ 15 ], cytotoxic necrotizing factor 1 (Cnf1) [ 16 ], hemolysin (HlyA) [ 16 ], uropathogenic specific protein (Usp) [ 17 ], and outer membrane protease T (OmpT) [ 18 ], are also shown as important virulence factors of E. coli in murine uropathogenesis. Carriage of these urovirulence factors is thought to enhance UPEC pathogenicity and is used to measure and categorize clinical UPEC strains isolated from different patient populations [ 19 , 20 , 21 ].…”

Anti-biofilm activity of caffeine against uropathogenic E. coli is mediated by curli biogenesis

“…The curli plays a vital role in the progression of UTIs caused by E. coli . It has been shown that curliated bacteria adhere better to the uroepithelial cells than bacteria without curli, as well as their ability to persist in urinary tracts, thus contributing to UTIs 10 , 12 , 13 , 49 , 50 . When Escherichia coli shifts from being planktonic to the sessile mode in biofilm, the flagellum formation stops, thereby boosting the production of curli fimbriae and polysaccharides to enhance adhesion between cells 9 , 13 , 51 .…”