Urinary Tract Infection: Pathogenesis and Outlook

Abstract

The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities.

Keywords: Escherichia coli; cystitis; pyelonephritis; urinary tract infection.

Figure 1. Clinical Features and Virulence Mechanisms in Cystitis and Pyelonephritis

UTIs can present clinically in a variety of ways, most often reflecting cystitis (infection of the bladder) or pyelonephritis (infection of the kidney). Uropathogenic Escherichia coli (UPEC) is the most common cause of UTI (especially among community-onset infections), among other pathogens. Selected virulence factors associated with the pathogenesis of UPEC cystitis or pyelonephritis are shown and include adhesins, siderophores, toxins, siderophores, capsule, and other systems (see text for details). UT: urinary tract.

Figure 2. Ribbon Representation of the Chaperone-Adhesin-Usher Complex for Assembly of Type 1 Pili from Escherichia coli

The periplasmic chaperone FimC (green) delivers structural subunits to the outer membrane usher (FimD, red) for assembly. Subunits shown represent the pilus tip structure and include the adhesin FimH (purple) and adapters FimG (yellow, within the barrel of FimD) and FimF (gray). Each subunit has its immunoglobulin-like fold completed by a strand provided by the next subunit, in a process called donor-strand complementation (DSC). The energetic favorability provided by this final structure drives assembly on the periplasmic side of the usher, as the periplasm is devoid of ATP. Protein Database PDB# 4J3O; adapted from [82].