Science1 publisher2 min readPublished
Texas A&M is hunting the genes that let UTI bacteria tolerate the body's copper
The plan is to find the genes that let urinary-tract bacteria survive the copper the body throws at them, then disable those genes so the immune response does the killing. No results from the new work yet.
The Scientist · Science desk
What happened
- A Texas A&M veterinary lab led by Sarguru Subash previously showed that the body pumps copper into the urinary tract during infection to kill the bacteria causing it, and that urine copper rises during a UTI.
- The group's new project will look at the genetic mechanisms that let UTI-causing bacteria tolerate the raised copper and keep growing anyway.
- The same project will study ceruloplasmin, a copper-carrying protein the lab's earlier findings suggest helps deliver copper to the infected tract.
- Copper is an essential nutrient for people and animals, and in the right environment and concentration it is also toxic to bacteria, which is the property the immune response uses.
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Why it matters
- capability A compound that only stripped copper tolerance would leave the killing to the patient's own immune response, so the same dose would do different amounts of work in different patients.
- constraint Copper itself cannot be pushed far as a therapy, because the body meters metal transport precisely to keep high concentrations from damaging its own cells, so the adjustable side is the bacterium's.
- decision Testing this idea forces a choice of endpoint: a compound that does nothing to bacterial growth in a tube may still lose the infection for the bacterium in a host whose copper delivery is intact.
Copper reaches the bacteria inside immune cells. Specialized cells of the innate response engulf invaders and expose them to an antimicrobial mixture that includes copper [6].
The bacteria have countermeasures. Because they meet copper in the environment, many species have evolved ways to remove or detoxify it [7]. Sarguru Subash says the mixture is what tips the balance. "Bacteria do have adaptations, but when it's presented in the context of this cocktail, the bacterial defense mechanisms are not as effective," he said [9].
The most testable of the early leads concerns attachment. Subash's team has early evidence that copper may do more than inhibit growth, interfering with fimbriae, the hairlike surface structures that let bacteria hold tightly to the cells lining the bladder [3]. Attachment is what keeps a bacterium in place against the tract's simplest defense. Bacteria that cannot attach firmly are more likely to be flushed out by urination, according to Subash [4].
The framing in the Texas A&M account is about infections that are getting harder to control with antibiotics [16]. The account describes previous findings and planned work; it does not name the bacterial species or the experimental system used [13]. Subash put the aim conditionally. "If we better understand how the bacteria overcome the host-imposed copper resistance, then we can develop therapies that make the bacteria more susceptible to copper and, more broadly, to everything that the immune system throws at them," he said [8].
The thing this does not tell you is whether copper tolerance decides the outcome of a real infection. A bacterium can carry tolerance genes and lose anyway, and it can lose for reasons that have nothing to do with the metal. Showing that removing those genes changes the course of an infection is the experiment the project is built to run, and the genetics of tolerance is the part still to be worked out [2]. Subash described the interaction as a tug-of-war between host and pathogen. "Sometimes the balance tips in favor of the host, so we can control the infections. Other times, the balance tips in favor of pathogens. As a result, we get clinical disease," he said [10].
What to watch
- Whether copper-tolerance mutants lose in a live urinary tract infection, not only in culture, is the result that would turn this from a hypothesis into a lever.
- Whether the fimbriae effect holds once growth rate is controlled, which would separate loss of attachment from general copper toxicity.
- Whether animals short of ceruloplasmin control UTIs worse; that would put copper delivery on the causal path.