Key Points
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Urinary tract infections (UTIs) are some of the most common bacterial infections and are caused by both Gram-negative and Gram-positive species. UTIs are categorized into uncomplicated and complicated, and are a severe public health problem; this situation is being exacerbated by the rise in multidrug-resistant strains.
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Uropathogens carry multiple virulence factors involved in the pathophysiology of UTIs. These virulence factors are involved in invasion and colonization, as well as in mediating the subversion of host defences.
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Knowledge about the mechanism of action of these virulence factors is being used to develop new therapeutics against UTIs.
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Therapies that are currently in the initial stages of development include vaccines targeting bacterial factors that are essential for initial attachment and disease progression (such as adhesins, toxins, proteases and siderophores), and small-molecule inhibitors that prevent adhesin–receptor interactions.
Abstract
Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host–pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
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Acknowledgements
The authors apologize to researchers whose work could not be included in this Review owing to space limitations. They thank members of S.J.H.'s and M.G.C.'s laboratories, especially K. W. Dodson, for their suggestions and comments. This work was supported by the 1F32DK104516-01 grant to A.L.F.-M. and the R01-DK051406, R01-AI108749-01 and P50-DK0645400 grants from the US National Institute of Allergy and Infectious Diseases (NIAID) and US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
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Glossary
- Pyelonephritis
-
A kidney infection characterized by cystitis symptoms with additional fever, flank pain, costovertebral-angle tenderness, nausea and vomiting.
- Cystitis
-
An infection of the bladder with accompanying symptoms of dysuria (painful urination), pain (particularly suprapubic), urinary frequency, urinary urgency and haematuria (blood in urine).
- Globosides
-
Glycosylceramides containing acetylated amino sugars and simple hexoses. These molecules are found in the kidneys.
- Lamellopodium
-
A cytoskeletal actin projection at the surface of a cell. In some cases, these actin-powered protrusions are a key factor driving cell motility.
- Teratogenicity
-
The capability of a compound to cause fetal malformation.
- Musculo-integumentary
-
Refers to the interaction between the muscular and integumentary systems. The muscular system is composed by the skeletal, smooth and cardiac muscles, whereas the skin, hair, nails and other specialized structures form the integumentary system.
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Flores-Mireles, A., Walker, J., Caparon, M. et al. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol 13, 269–284 (2015). https://doi.org/10.1038/nrmicro3432
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DOI: https://doi.org/10.1038/nrmicro3432
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