Uropathogenic E. coli form intracellular bacterial communities in the outermost cell layer of an infected bladder. Image courtesy of Scott Hultgren.
Like jet-setting celebrities with homes in more than one location, some pathogenic strains of E. coli make two different places in the human body their homes. In a paper just out in the journal Science Translational Medicine, researchers describe how recurrent urinary tract infections in women may be caused by E. coli strains that can reside in both the gut and bladder.
Ecologically speaking, organisms are thought to adapt to a particular environment and learn how to best survive in that environment’s conditions. The trade-off is the adaptation to that particular environment comes at a cost: The organism is less fit to survive elsewhere.
However, the latest work by a team led by Jeffrey Gordon at Washington University in St. Louis suggests that may not be the case for some strains of E. coli that cause recurrent UTIs in women. These strains happily thrive both in the gut and bladder and can move easily between the two. “These experiments suggest that the organisms may not have to have a huge fitness cost for living in both habitats,” says Gordon. The work points to “another dimension of thinking about the origins of recurrent UTIs.”
In collaboration with Scott Hultgren’s group, also at Washington University in St. Louis, Gordon’s team studied four women who suffered from three consecutive UTIs each. These women were part of a large clinical trial looking into recurrent UTIs. Fecal and urine samples were collected during each of the women’s three UTI episodes. “We wanted to compare each woman to herself as recurrent infections occurred,” explains Gordon. “We asked the question: At any given infection, was there a population of disease-causing microbes, in this case uropathogenic E. coli, that dominated the urinary tract and also were represented in the gut?”
The investigators collected 45 different strains of pathogenic E. coli and carried out multilocus sequence typing and whole genome sequencing. They found that two of the women had the same strains dominate both the gut and bladder in each of their three infections. The other two women each had a shift in the type of strain that occurred in both body habitats between episodes of recurrent UTI. “In one of the women, not only was there whole-scale shift in the types of strain, but the strain that was seen in the last episode resembled a strain found in the other individual who had maintained that strain throughout the three episodes,” says Gordon.
Next, the investigators placed the strains from the woman that underwent a whole-scale shift in mouse models and analyzed the changes that took place in the bacteria. They discovered that the strain that dominated the last UTI episode had increased fitness relative to the earlier strain in both the gut and the bladder.
Pathogenic E. coli strains have evolved a variety of strategies to cause recurrent UTIs in women. One involves formation of intracellular bacterial communities in the bladder wall. These communities can remain quiet, or they can release bacteria to cause infection.
Taken together, Gordon says, the data argue that recurrent UTIs should be viewed from a more holistic perspective. “We have to look at the human body as an ecosystem where very different body habitats can harbor organisms that promote health while, at the same time, contain organisms that can cause disease,” says Gordon. “At least two body habitats, and the spaces between them, such as the periurethral area, should be considered when hunting for the homes of lurking uropathogenic E. coli that cause recurrent bladder infections.”
