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Bacteria Behind UTIs Make Their Own DNA Building Blocks From Your Urine

18 MARCH 2021

Some infectious bacteria have adapted so well to the human bladder, they appear to make their own DNA using chemicals in our urine.

The urinary tract is a hard place for most bacteria to survive. That's why urine is often said to be sterile, although that's not actually true

 

Just like your gut, human urine is home to a community of microbes, known as a microbiota, and while most bacteria that live within it are harmless, sometimes a particular species can tip the scales, causing painful urinary tract infections (UTIs).

Streptococcus agalactiae is a known source of UTIs in some humans, and new research has now revealed how it can survive in such an unfriendly environment.

In a healthy human body, urine should be relatively low in the four nucleobases making up DNA's code, which are broken down into nitrogenous compounds and excreted out.

Sequencing the S. agalactiae genome, scientists have now found a key, specialized gene, which allows the bacterium to exploit the presence of other compounds in our urine to produce at least one of these bases - guanine - in order for it to survive.

Similar genes have also recently been found in Escherichia coli (E. coli), which is the most common offender of human UTIs. 

Usually, in the gut or the blood, E. coli and Streptococcus scavenge for certain chemicals they need to make DNA, borrowing products like guanine from our own bodies. In the urinary tract, however, these essential building blocks are ultimately broken down into uric acid, which means they are not as easy to find.

 

It's a tough situation, 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 that not many organisms can live in," explains molecular geneticist Matthew Sullivan from Griffith University in Australia.

"It seems to be a common strategy among species of bacteria that make up the microbiome of the urine."

In the study, scientists used mice to show how essential this specialized gene, known as guaA, truly is. Collecting Streptococcus strains from several individuals, researchers compared a normal S. agalactiae infection with a form of the bacterium deficient in guaA.

Microbes that were unable to create their own guanine were unable to colonize the bladder of mice to the same extent. The same thing was found when researchers used synthetic human urine.

This suggests guaA is essential for a Streptococcus infection to take hold in the bladder, not just in mice but also in us.

When researchers added extra guanine to the urine, even bacterial strains without the metabolic pathways to create guanine on their own were able to survive and thrive, which suggests this base is an essential limiting factor.

 

Compared to E. coli, Streptococcus shows key differences in the way it controls guaA genes, but the outcomes appear quite similar and give us a new avenue for treating UTIs, which have been growing ever more resistant to available antibiotics. 

Already, techniques that target guanine synthesis elsewhere in the body have helped beat back other forms of Streptococcus bacteria. 

While not nearly as common as E. coli infections of the bladder, Streptococcus causes roughly 160,000 UTIs each year in the US, and these can prove difficult to treat, especially since we don't know a lot about how the infection works. 

What's more, because Streptococcus UTIs often show up in those who are pregnant, the elderly, and patients with underlying health conditions like diabetes, finding safe and effective treatment options becomes even trickier.

"Research like this gives us new opportunities to develop alternative treatments in a world with increasing antibiotic resistance due to overuse of existing medicines. For example, we could target this pathway in efforts to design new drugs to prevent infection," explains Sullivan.

"Overall, the study illuminates the importance of fundamental discoveries that help us perceive how microorganisms interact with humans."

The study was published in the International Society of Microbial Ecology (ISME) Journal.