Role of aggregate-forming pilus (AFP) in adherence and colonization of both intestinal and urinary tracts

Abstract

Hybrid-pathogenic Escherichia coli represent an important group of strains associated with intestinal and extraintestinal infections. Recently, we described strain UPEC-46, a uropathogenic/enteroaggregative E. coli (UPEC/EAEC) strain presenting the aggregative adherence (AA) pattern on bladder and colorectal epithelial cells mediated by aggregate-forming pili (AFP). However, the role of AFP and other uninvestigated putative fimbriae operons in UPEC-46 pathogenesis remains unclear. Thus, this study evaluated the involvement of AFP and other adhesins in uropathogenicity and intestinal colonization using different in vitro and in vivo models. The strain UPEC-46 was able to adhere and invade intestinal and urinary cell lines. A library of transposon mutants also identified the involvement of type I fimbriae (TIF) in the adherence to HeLa cells, in addition to colorectal and bladder cell lines. The streptomycin-treated mouse in vivo model also showed an increased number of bacterial counts in the colon in the presence of AFP and TIF. In the mouse model of ascending urinary tract infection (UTI), AFP was more associated with kidney colonization, while TIF appears to mediate bladder colonization. Results observed in in vivo experiments were also confirmed by electron microscopy (EM) analyses. In summary, the in vitro and in vivo analyses show a synergistic role of AFP and TIF in the adherence and colonization of intestinal and urinary epithelia. Therefore, we propose that hybrid E. coli strains carrying AFP and TIF could potentially cause intestinal and urinary tract infections in the same patient.

FimH of uropathogenic Escherichia coli influenced the infection in prostate cells by the modulation of JAK/STAT signaling pathway

“…Aggregate-forming pili (AFP) and type I mbriae (TIF) have synergistic effects on the adhesion and colonization of intestinal and urinary epithelial cells; therefore, mixed E. coli strains possessing AFP and TIF may infect both the intestinal and urinary tracts and are therefore more di cult to treat. [43] However, whether testosterone can be used as an anti-infective agent for defending UPEC to continuously infect prostate epithelial cells, especially against strains with strong virulence factors, such as FimH, remains to be further studied. In conclusion, our study indicates that testosterone can be used to treat clinical recurrent UPEC infection and persistent prostatitis.…”

Adhesin related genes as potential markers for the enteroaggregative Escherichia coli category

“…Also important to note that 100% of these 74 AAF+ strains were aggR + and presented AA pattern in HeLa cells adherence assays, while 100% of AFP+ strains were aggR- . While the role of AAF in pathogenesis and as a specific EAEC marker is well stablished, recent data showed that AFP has emerged as an important virulence trait in a subset of EAEC strains carrying aat , aai and aap ( Lang et al., 2018 ; Dias et al., 2020 ; Schüroff et al., 2021 ; Schüroff et al., 2022 ). Considering our results, and the EAEC classification proposed by Kaper et al.…”

“…This plasmid (pAFP) also carried a new adhesin named aggregative-forming pilus (AFP) encoded by the afp operon, which among its components carries an AraC-like regulator very similar to aggR , named afpR . AFP was shown to be involved in bacterial piliation, autoaggregation, adhesion and cytotoxicity ( Lang et al., 2018 ) and was recently observed mediating AA in a hybrid enteroaggregative/uropathogenic E. coli (EAEC/UPEC) strain ( Schüroff et al., 2021 ; Schüroff et al., 2022 ). Moreover, phylogenetic analyses have shown that AFP-positive strains carrying other virulence genes related to EAEC pathogenesis ( aat operon, type 6 secretion system genes and aap ), are clustered with other fecal EAEC strains ( Schüroff et al., 2021 ).…”