Some infectious bacteria have adapted so well to the human bladder that they appear to make their own DNA by using chemicals in our urine.
The urinary tract is a difficult place for most bacteria to survive. Therefore, it is often said that urine is sterile, although it is not actually true.
Like your gut, human urine is home to a community of microbes known as a microbiota, and while most bacteria living in it are harmless, a specific species can sometimes cause the scales to tip over and painful urinary tract infections ( UTIs).
Streptococcus agalactiae is a known source of UTIs in some people, and new research has now revealed how it can survive in such an unfriendly environment.
In a healthy human body, urine must be relatively low in the four nucleobases that make up the DNA code, which are broken down into nitrogen compounds and excreted.
Sequence of the S. agalactiae genome, scientists have now found an important, specialized gene that enables the bacterium to utilize the presence of other compounds in our urine to produce at least one of these bases – guanine – in order to survive.
Similar genes have also been recently found in Escherichia coli (E. coli), which is the most common offender of human UTIs.
Usually in the intestines or in the blood, E coli and Streptococcus looking for certain chemicals they need to make DNA, and borrowing products like guanine from our own bodies. In the urinary tract, however, these essential building blocks are eventually broken down into uric acid, which means that it is not so easy to find.
This is a difficult situation, and it means both E coli and Streptococcus must synthesize their own chemical bases if they are to grow and reproduce.
“It’s basically a survival strategy to colonize the urine, an environment where not many organisms can live,” explains molecular geneticist Matthew Sullivan of Griffith University in Australia.
“This 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, really is. Collect Streptococcus of different individuals, researchers compared a normal S. agalactiae infection with a form of the bacterium with a deficiency of guaA.
Microbes that could not create 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 a Streptococcus infection to take hold in the bladder, not only in mice but also in us.
When researchers added extra guanine to the urine, even bacterial strains without the metabolic pathways to create guanine alone could survive and thrive, suggesting that this base is a vital limiting factor.
In comparison with E coli, Streptococcus shows significant differences in the way it controls guaA genes, but the outcomes look very much the same and give us a new way of treating UTIs that are increasingly resistant to available antibiotics.
Techniques aimed at guanine synthesis elsewhere in the body have already helped other forms of Streptococcus bacteria.
Although not nearly as common as E coli bladder infections, Streptococcus causes about 160,000 UTIs a year in the US, and it can be difficult to treat, especially since we do not know much about how the infection works.
What’s more, because Streptococcus UTIs often appear in those who are pregnant, the elderly, and patients with underlying health conditions such as diabetes, and find it even more difficult to find safe and effective treatment options.
“Research like this offers us new opportunities to develop alternative treatments in a world with increasing resistance to antibiotics due to overuse of existing medicines. For example, we can pave the way in efforts to design new medicines to prevent infection,” he explains. Sullivan.
“Overall, the study highlights the importance of fundamental discoveries that help us see how microorganisms interact with humans.”
The study is in the International Society of Microbial Ecology (ISME) Journal.