Waging War against UropathogenicEscherichia coli: Winning Back the Urinary Tract

Abstract

Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is a substantial economic and societal burden-a formidable public health issue. Symptomatic UTI causes significant discomfort in infected patients, results in lost productivity, predisposes individuals to more serious infections, and usually necessitates antibiotic therapy. There is no licensed vaccine available for prevention of UTI in humans in the United States, likely due to the challenge of targeting a relatively heterogeneous group of pathogenic strains in a unique physiological niche. Despite significant advances in the understanding of UPEC biology, mechanistic details regarding the host response to UTI and full comprehension of genetic loci that influence susceptibility require additional work. Currently, there is an appreciation for the role of classic innate immune responses-from pattern receptor recognition to recruitment of phagocytic cells-that occur during UPEC-mediated UTI. There is, however, a clear disconnect regarding how factors involved in the innate immune response to UPEC stimulate acquired immunity that facilitates enhanced clearance upon reinfection. Unraveling the molecular details of this process is vital in the development of a successful vaccine for prevention of human UTI. Here, we survey the current understanding of host responses to UPEC-mediated UTI with an eye on molecular and cellular factors whose activity may be harnessed by a vaccine that stimulates lasting and sterilizing immunity. MISSION: ERADICATE UPEC-MEDIATED UTIUrinary tract infection (UTI) is one of the most common infections in humans. Bacteria present in fecal matter inoculate the periurethral area, then the bladder (124, 176, 291), causing symptoms clinically termed cystitis. Left untreated, bacteria ascend the ureters to the kidney and establish a secondary infection, acute pyelonephritis. At this juncture, there is risk of permanent renal scarring, and bacteria can access the bloodstream (282). It is estimated that 40% of women and 12% of men will experience a symptomatic UTI, with incidences peaking in their early 20s or after age 85, respectively (75, 185). Approximately 25% of these women will experience recurrence within 6 to 12 months (75, 185). Uropathogenic Escherichia coli (UPEC) is the most common etiological agent responsible for uncomplicated UTI (93, 94,282). Uropathogenic strains are classified as extraintestinal pathogenic E. coli, a broad grouping of E. coli that cause diseases other than gastroenteritis and typically lack a type III secretion system (171,220,221,283,284). Nonetheless, UPEC strains express an assortment of virulence and fitness factors that aid in successful colonization of the mammalian urinary tract (126,136). In the United States alone, the estimated annual societal cost of UTI is more than 3 billion dollars (159).Despite a relatively in-depth knowledge base for UPEC physiology and virulence mechanisms (reviewed in references 54, 126, 136, and 284), no licensed vaccine to prevent UTI exists in the Un...

Siderophore vaccine conjugates protect against uropathogenicEscherichia coliurinary tract infection

“…In Europe, two vaccines against UTIs called SolcoUrovac and Uro-Vaxom are licensed for use in women with recurrent UTIs (16). SolcoUrovac is a vaginal suppository containing 10 heat-killed UPEC strains that provides relatively poor protection in the absence of frequent administration (17).…”

Molecular mechanism of bacterial type 1 and P pili assembly

“…It has been shown that bacterial pathogens deficient in type I or P pili are strongly attenuated in their ability to cause UTIs [65]. A major aim of studying the nanomachines involved in bacterial pathogenesis is to exploit the detailed structural knowledge to move from the current non-specific antibiotic treatments causing growing problems with resistance and therefore with chronic infections to more specific treatments targeting virulence factors.…”

Microbiological Quality of a Locally Brewed Alcoholic Beverage (Pito) Sold in a Community within the Greater Accra Region, Ghana

“…It is part of the normal flora of the intestine of human and vertebrates. In spite of this, some strains of E. coli can cause gastroenteritis, urinary tract infection [31] as well as diarrhoea in infant [32]. Therefore, identification of this bacterium in the pito samples could merit public health attention.…”