Association between TLR4 polymorphisms (896 A>G, 1196 C>T, - 2570 A>G, - 2081 G>A) and virulence factors in uropathogenic Escherichia coli.

Abstract

Escherichia coli is the main etiological agent of urinary tract infections. Its virulence factors are important during the initial interaction stage with the host as they enable colonization of urinary tract tissues. The genetic markers evidencing susceptibility to develop recurrent infections have been previously described. Toll-like receptors are critical sensors of microbial attacks, and they are also effectors of the individual's innate defense for elimination of pathogens. The aim of this study was to evaluate the association between functional polymorphisms (896 A>G, 1196 C>T, - 2570 A>G, - 2081 G>A) and susceptibility to develop urinary tract infections as well as E. coli virulence factors. This study includes 100 samples from patients diagnosed with UTI and 100 samples from uninfected subjects. A conventional urine culture was performed and the isolates were identified by using the Vitek automated system. TLR4 gene polymorphisms were identified by the PCR-RFLP technique. The hlyA, fimH, papC, iutA and cnf1 virulence factors as well as the E. coli phylogenetic group were assessed by PCR. In this study, it was observed that the presence of the - 2570 polymorphism represents a risk of UTI (p < 0.01), whereas - 2081 confers protection (p < 0.01). The 896A>G and 1196C>T polymorphisms were associated with the E. coli virulence factors fimH and hlyA, respectively (p < 0.05). The B2 group was the most frequent in clinical isolates (51%), and it displayed more virulence factors regarding other phylogenetic groups (p ≤ 0.05). An interesting finding was that strains considered as commensals, belonging to groups A and B1, can cause UTI and present virulence factors. Polymorphisms occurring in the TLR4 promoter region are correlated with susceptibility or risk of UTI, whereas structural polymorphisms are associated with the recognition of virulence factors displayed by E. coli.