Abstract
Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host with the capacity for high-throughput analysis. Then, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the simple pathogenicity assay. From the screening, several virulence factors (VFs) involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. The results demonstrated, the simple assay with C. elegans was useful as a UPEC infectious model. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.
Highlights
Urinary tract infections (UTIs) are very common [1], and the resulting direct medical cost is substantial [2]
For the Uropathogenic E. coli (UPEC) study, the results revealed that the pathogenicity in C. elegans was associated with the number of virulence factors (VFs), which were identified as virulence genes involved in the pathogenicity in mammals [11]
Most of the UTI-associated isolates belonged to the B2 group, which mainly consists of extraintestinal pathogenic strains that display a high concentration of VFs [3]
Summary
Urinary tract infections (UTIs) are very common [1], and the resulting direct medical cost is substantial [2]. Uropathogenic E. coli (UPEC) is one of the major etiologies of UTIs. A UPEC strain usually requires an array of virulence factors (VFs) with different functions to invade the urinary tract. The VFs of pathogenic bacteria are potential antimicrobial targets and markers of the pathogen. Different UPEC strains may harbor varying combinations of VFs, and most of the factors only exist in a fraction of UPEC strains [3]. A combination of multiple VFs is required for developing effective and widely usable measures to prevent or treat UTIs caused by UPEC. Identifying how VFs contribute to UTIs and understanding their epidemiological distribution would facilitate the development of such novel strategies to manage the infection
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