Urinary tract infections

Abstract

Urinary tract infections (UTIs) are among the most common bacterial infections and generally occur when uropathogens, normally quiescent residents of the gastrointestinal tract, enter the urinary tract. Cystitis, caused by uropathogens that colonize the lower urinary tract, is usually self-limiting and amenable to antibiotic therapy. In spite of this, uropathogens can gain access to the upper urinary tract, causing pyelonephritis, and may enter the bloodstream from this site, causing potentially fatal urosepsis. The vast majority of UTIs are caused by uropathogenic Escherichia coli (UPEC), a heterogenous group of E. coli strains. Other organisms that cause UTIs include Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus. All of these organisms have a variety of virulence factors, often encoded on large, horizontally acquired pathogenicity islands, which promote growth in urine, colonization of the host urinary tract, and evasion of the host immune system. These virulence factors include a plethora of distinct fimbrial and non-fimbrial adhesins, flagella, ureases, osmolarity and pH homeostasis factors, nutrient transporters, extracellular polysaccharides, metal scavenging systems, an assortment of toxins, an array of bacteriocins, and envelope damage response systems. Uropathogens also have sophisticated genetic regulatory mechanisms to coordinate expression of these virulence factors. This is especially true between diverse fimbrial operons and between fimbrial and flagella operons. However, no one preeminent set of virulence factors exists among uropathogens, which instead use combinations of the aforementioned virulence factors to facilitate uropathogenesis. Thus, a broad understanding of these virulence factors is necessary to gain a comprehensive understanding of uropathogenesis and UTIs.