Urinary Tract Infections Caused by Uropathogenic Escherichia coli: Mechanisms of Infection and Treatment Options

Abstract

Urinary tract infections (UTIs) are common bacterial infections that represent a severe public health problem. They are often caused by Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumonia), Proteus mirabilis (P. mirabilis), Enterococcus faecalis (E. faecalis), and Staphylococcus saprophyticus (S. saprophyticus). Among these, uropathogenic E. coli (UPEC) are the most common causative agent in both uncomplicated and complicated UTIs. The adaptive evolution of UPEC has been observed in several ways, including changes in colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. While antibiotic therapy has historically been very successful in controlling UTIs, high recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly reduce the efficacy of these treatments. Furthermore, the gradual global emergence of multidrug-resistant UPEC has highlighted the need to further explore its pathogenesis and seek alternative therapeutic and preventative strategies. Therefore, a thorough understanding of the clinical status and pathogenesis of UTIs and the advantages and disadvantages of antibiotics as a conventional treatment option could spark a surge in the search for alternative treatment options, especially vaccines and medicinal plants. Such options targeting multiple pathogenic mechanisms of UPEC are expected to be a focus of UTI management in the future to help combat antibiotic resistance.

Keywords: alternative treatment options; urinary tract infections; uropathogenic Escherichia coli.

Figure 1

Epidemiology of urinary tract infections (UTIs). UTIs are multispecies; the type of infection can be caused by Gram-negative bacteria, Gram-positive bacteria, or fungi. Among them, uropathogenic E. coli (UPEC) are the main pathogenic factor for UTIs, accounting for about 75% of uncomplicated UTI cases and more than half of complicated UTI cases.

Figure 2

Pathogenesis of UTIs and uropathogenic E. coli (UPEC) adhesin structure. UTIs begin when UPEC induce periurethral invasion and colonization. Subsequent UPEC ascension into the bladder and expression of fimbriae and adhesins result in colonization and invasion of host cells and interaction with the defensive system of the bladder epithelium. UPEC produce toxins that induce host cell damage, releasing essential nutrients that promote bacterial survival and ascension to the kidneys. Kidney colonization further leads to bacterial toxin production and host tissue damage. In severe cases, it can lead to the occurrence of diseases such as bacteremia. In the abovementioned process, the structure of UPEC, including type 1 fimbriae, P fimbriae, and other fimbriae and non-fimbrial adhesins, plays an important role in the pathogenic process of UPEC.

Figure 3

Adhesins of uropathogenic bacteria (orange: organism; blue: assembly pathway; green: adhesins).

Figure 4

Schematic structure of type 1 fimbrial and P fimbrial organelles in UPEC.

Figure 5

The formation of intracellular bacterial communities (IBCs). E. coli enter the cytoplasm of urothelial cells and then form IBCs. The rapidly multiplying E. coli initially adopt a coccoid morphology and then change back to a rod-like shape as the IBC mature. Finally, E. coli protrude from the original cells and colonize and invade nearby cells in the form of filaments, initiating a second round of IBC formation.

Figure 6

Resistance profiles for uropathogens.

Figure 7

Structural formulae of some UPEC-resistant and UPEC-susceptible antibiotics (orange: UPEC resistant; purple: UPEC susceptible).