The recently published findings may open new avenues for treating urinary tract infections.
Dietary metabolites and urine acidity may affect the growth of bacteria in the urinary tract, potentially opening new avenues for treating urinary tract infections, according to a new study published in The Journal of Biological Chemistry (2015; 290:15949-60).
To investigate the body’s natural defenses against UTI, researchers at Washington University in St. Louis cultured Escherichia coli bacteria in urine from healthy volunteers and compared how effectively the antimicrobial protein siderocalin (SCN) hampered bacterial growth in different samples. During UTIs, cells in the urinary tract secrete SCN to inhibit bacterial proliferation by interfering with uptake of iron that the bacteria need to grow. SCN activity varies widely from person to person.
The authors considered what characteristics in the urine of healthy volunteers might influence the antimicrobial effectiveness of SCN. They found that elevated urine pH and small molecules called aryl sulfates, produced when gut microbes metabolize food, exerted a strong effect on SCN’s antibacterial activity.
Changing pH by itself promoted or inhibited bacterial growth in urine, the study showed, which could affect therapy for UTI. Acid urine has long been thought to reduce bacterial growth, but surprisingly, less acidic urine, with a pH closer to neutral, had a stronger effect on SCN activity than more acidic samples.
In addition to pH, certain metabolites, specifically aryl sulfates, are key to controlling SCN activity, the authors determined after evaluating thousands of compounds in the urine samples. These metabolites, which vary with diet, were more plentiful in samples with less bacterial growth.
The authors surmise that SCN may work with aryl metabolites from dietary plant compounds to prevent E. coli from using a compound called enterobactin to bind to iron in urine. Exploring methods of obstructing enterobactin’s iron-binding capacity could lead to eventual development of drugs with different antimicrobial properties than current antibiotics, they note.
“Our study suggests that the body’s immune system harnesses dietary plant compounds to prevent bacterial growth,” said senior author Jonathan Henderson, MD, PhD, in a press release from Washington University. “We identified a list of compounds of interest, and many of these are associated with specific dietary components and with gut microbes.”
Finding new approaches to preventing and treating UTI by promoting the chemical characteristics of urine that restrict bacterial growth, thereby strengthening the body’s innate immune defenses, could help address the problem of growing resistance to the antibiotics used to treat UTI, the study suggests.
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