Uropathogenic Escherichia coli: The Pre-Eminent Urinary Tract Infection Pathogen pp. 1-66
Authors: (David W. Hilbert, Women’s Health Research Center, Medical Diagnostic Laboratories, Hamilton, New Jersey, USA)
Abstract: Community-acquired urinary tract infections (UTIs) are a major health problem, largely affecting women. In the United States, 11% of women suffer a UTI each year, and 60% of women experience at least one UTI during their lifetime. Recurrence is common, with 44% of patients suffering another infection within 1 year. Most infections remain confined to the bladder and cause painful and urgent urination (cystitis), although some patients are colonized asymptomatically. In a subset of infections, the pathogen ascends to the kidneys, resulting in pyelonephritis, a serious and life-threatening condition. Uropathogenic Escherichia coli (UPEC) is responsible for >80% of community-acquired UTIs. UPEC originate in the gastrointestinal (GI) tract and are transmitted to the urinary tract via colonization of the vagina and periurethral area. UPEC utilizes a number of virulence factors to colonize the urinary tract, including fimbriae to adhere to and invade the bladder epithelium, siderophores to scavenge iron, and toxins to modify host cell signaling. These virulence factors are required to overcome the formidable innate immune defenses of the bladder. Toll-like Receptors (TLRs), especially TLR4, sense UPEC and trigger a multifaceted response to combat the infection, including secretion of chemokines to recruit neutrophils, antimicrobial peptide (AMP) secretion and exfoliation of the bladder epithelium. The sequencing of UPEC genomes has revealed a highly mosaic structure with numerous pathogenicity islands (PAIs) integrated at multiple sites in the genome. In addition, comparative genomics has revealed a close relationship between UPEC and other pathogenic E. coli, including strains that cause avian colibacillosis and neonatal meningitis. Although most UTIs can be treated with standard antimicrobial therapy, resistance to these agents is rising. The search for new therapies has led to both the innovation of novel molecules to inhibit UPEC adherence as well as the revisiting of older agents such as fosfomycin. Prevention of UTIs has focused on cranberry consumption and the use of probiotics to prevent vaginal colonization by UPEC. Lastly, progress has been made on development of a vaccine to prevent UTIs. In summary, UTIs caused by E. coli are a major health problem, with researchers using a multidisciplinary approach to improve prevention and therapy.
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