Abstract
Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infection (UTI), a widespread infectious disease of great impact on human health. This is further emphasized by the rapidly increase in antimicrobial resistance in UPEC, which compromises UTI treatment. UPEC biology is highly complex since uropathogens must adopt extracellular and intracellular lifestyles and adapt to different niches in the host. In this context, the implementation of forefront ‘omics’ technologies has provided substantial insight into the understanding of UPEC pathogenesis, which has opened the doors for new therapeutics and prophylactics discovery programs. Thus, ‘omics’ technologies applied to studies of UPEC during UTI, or in models of UTI, have revealed extensive lists of factors that are important for the ability of UPEC to cause disease. The multitude of large ‘omics’ datasets that have been generated calls for scrutinized analysis of specific factors that may be of interest for further development of novel treatment strategies. In this review, we describe main UPEC determinants involved in UTI as estimated by ‘omics’ studies, and we compare prediction of factors across the different ‘omics’ technologies, with a focus on those that have been confirmed to be relevant under UTI-related conditions. We also discuss current challenges and future perspectives regarding analysis of data to provide an overview and better understanding of UPEC mechanisms involved in pathogenesis which should assist in the selection of target sites for future prophylaxis and treatment.
Highlights
1.1 Extraintestinal Pathogenic Escherichia coliExtra intestinal pathogenic Escherichia coli (ExPEC) encompass those E. coli strains that are able to cause infection outside the intestine (Kaper et al, 2004)
Chen et al used bioinformatics tools to find genes positively selected among seven different uropathogenic E. coli (UPEC) genomes and found that genes involved in cell wall/membrane biogenesis, secondary metabolites biosynthesis as well as replication, recombination and repair were common to all strains tested (Chen et al, 2006)
The results revealed that the genes present in the high-pathogenicity island (HPI) allow for flexible adaptation of UPEC to several growth environments, and that the UPEC strain UTI89 displays remarkable metabolic homeostasis compared to a non-UPEC strain (Yan et al, 2015)
Summary
Extra intestinal pathogenic Escherichia coli (ExPEC) encompass those E. coli strains that are able to cause infection outside the intestine (Kaper et al, 2004). ExPEC isolates are facultative pathogens: they reside as commensals in the gut and belong to the normal microbiota, while outside the intestine are mainly related to neonatal meningitis and urinary tract infections (UTIs) in humans (Kohler and Dobrindt, 2011). They can be distinguished from the commensal and intestinal pathogenic E. coli by various genotyping methods, phylogrouping and multilocus sequence typing (MLST). Nowadays this classification is considered outdated, since isolates within the specific groups have been shown to cause infections at other sites (Dale and Woodford, 2015) and they overlap in the phylogenetic analysis (Jørgensen et al, 2019)
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