The acidity of urine -- as well as the presence of small molecules related to diet -- may influence how well bacteria can grow in the urinary tract, a new study shows.
Urinary tract infections (UTIs) often are caused by a strain of bacteria called Escherichia coli (E. coli), and doctors long have relied on antibiotics to kill the microbes. But increasing bacterial resistance to these drugs is leading researchers to look for alternative treatment strategies.
"Many physicians can tell you that they see patients who are particularly susceptible to urinary tract infections," said senior author Jeffrey P. Henderson, M.D., Ph.D., assistant professor of medicine at Washington University School of Medicine in St. Louis. "We often don't know why certain people seem to be prone to recurrent UTIs. For a long time, we had inexpensive antibiotics that worked really well for this. But over the last 10-15 years, we have seen a huge jump in bacterial infections that are resistant to many of these drugs."
With this in mind, the team studied how the body naturally fights bacterial infections. They cultured E. coli in urine samples from healthy volunteers and noted major differences in how well individual urine samples could harness a key immune protein to limit bacterial growth.
"We could divide these urine samples into two groups based on whether they permitted or restricted bacterial growth," Henderson said. "Then we asked, what is special about the urine samples that restricted growth?"
The urine samples that prevented bacterial growth supported more activity of this key protein, which the body makes naturally in response to infection, than the samples that permitted bacteria to grow easily. The protein is called siderocalin, and past research has suggested that it helps the body fight infection by depriving bacteria of iron, a mineral necessary for bacterial growth. Their data led the researchers to ask if any characteristics of their healthy volunteers were associated with the effectiveness of siderocalin.
Age and sex did not turn out to be major players. Of all the factors they measured, the only one that was really different between the two groups was pH -- how acidic or basic the urine was.
Henderson said that conventional wisdom in medicine favors the idea that acidic urine is better for restricting bacterial growth. But their results were surprising because samples that were less acidic, closer to the neutral pH of pure water, showed higher activity of the protein siderocalin and were better at restricting bacterial growth than the more acidic samples.
Importantly, the researchers also showed that they could encourage or discourage bacterial growth in urine simply by adjusting the pH, a finding that could have implications for how patients with UTIs are treated.
Citation: Shields-Cutler RR, Crowley JR, Hung CS, Stapleton AE, Aldrich CC, Marschall J, Henderson JP. Human urinary composition controls siderocalin's antibacterial activity. The Journal of Biological Chemistry. June 26, 2015.