Some infectious bacteria have adapted so well to the human bladder that they appear to make their own DNA from chemicals in our urine.
The urinary tract is a difficult place to survive for most bacteria. That is why it is often said that urine is sterile, although that is not true.
Like your gut, human urine is home to a community of microbes known as a microbiota, and while most of the bacteria living in it are harmless, sometimes a particular strain can tip the scales and cause painful urinary tract infections (UTIs).
Streptococcus agalactiae is a known source of UTIs in some people, and new research has now shown how it can survive in such an unfriendly environment.
In a healthy human body, the urine should be relatively low in the four nucleobases that make up the DNA code, which are broken down into nitrogen compounds and excreted.
Series of the S. agalactiae genome, scientists have now found an important, specialized gene that allows the bacteria to exploit the presence of other compounds in our urine to produce at least one of these bases – guanine – for survival.
Similar genes have also recently been found in Escherichia coli (E. coli), the most common culprit of human UTIs.
Usually, in the gut or blood, E coli and Streptococcus searching for certain chemicals they need to make DNA by borrowing products such as guanine from our own body. In the urinary tract, these essential building blocks are eventually broken down into uric acid, making them not so easy to find.
It’s a fix, and it means both E coli and Streptococcus must synthesize their own chemical bases if they want to grow and reproduce.
“It’s basically a survival strategy to colonize the urine, an environment in which not many organisms can live,” explains molecular geneticist Matthew Sullivan of Griffith University in Australia.
“It appears to be a common strategy among bacteria species that make up the urine microbiome.”
In the study, scientists used mice to show just how essential this specialized gene, known as guaA, really is. Collect Streptococcus strains from different individuals, researchers compared a normal S. agalactiae infection with a form of the bacteria deficient in guaA.
Microbes unable to make their own guanine could not colonize the bladder of mice to the same extent. The same was found when researchers used synthetic human urine.
This suggests that guaA is essential for one Streptococcus infection to settle in the bladder, not only in mice but in us as well.
When researchers added extra guanine to the urine, even strains of bacteria without the metabolic pathways to make guanine on their own were able to survive and thrive, suggesting that this base is an essential limiting factor.
As compared to E coli Streptococcus shows important differences in the way it controls guaA genes, but the results are quite similar and give us a new path to treating UTIs, which have become increasingly resistant to available antibiotics.
Although techniques aimed at guanine synthesis elsewhere in the body have helped other forms of it Streptococcus bacteria.
Although not nearly as common as E coli infections of the bladder, Streptococcus causes about 160,000 UTIs in the US annually, and these can prove to be difficult to treat, especially since we don’t know much about how the infection works.
What’s more, because Streptococcus UTIs are common in pregnant women, the elderly, and patients with underlying health conditions such as diabetes, finding safe and effective treatment options becomes even more difficult.
“Research like this gives us new opportunities to develop alternative treatments in a world of increasing antibiotic resistance due to overuse of existing drugs. For example, we could focus on this path when designing new drugs to prevent infection,” explains Sullivan explains.
Overall, the study highlights the importance of fundamental discoveries that help us see how microorganisms interact with humans.
The study is published in the International Society of Microbial Ecology (ISME) Journal