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E. coli Bacteria Exploit Copper to Fuel UTIs

AUG 04, 2017 | MICHAELA FLEMING
A new study conducted by Washington University School of Medicine in St. Louis reports that Escherichia coli (E. coli) bacteria are commandeering copper ions to strengthen bacteria levels in hard-to-treat urinary tract infections (UTIs). The results from this study, published in Nature Chemical Biology, present possible alternatives to the typical antibiotic treatment of UTIs. Scientists hypothesize that cutting off access to copper ions will reduce the strength of E. coli bacteria and therefore reduce the power of UTIs.

Copper ions enter the body through various foods such as grains, nuts, and shellfish. High concentrations of copper were previously acknowledged for eliminating bacteria in the body. In the past, researchers have studied E. coli connected to UTIs, but were unable to determine how the bacteria uses the copper ions in urine. The studies revealed that a molecule called yersiniabactin (Ybt)—not only found in E. coli, but also in other invasive bacteria—seizes the copper and prevents it from growing to antibacterial levels. Until now, however, researchers did not know what the bacteria does with the bound copper. Prior studies have revealed that bacteria can import iron into the cell; however, it was long thought that E. coli lack a method to be able to import copper. In addition, researchers assumed that Ybt could only import iron.

The researchers of the Nature study, including Jeffery P. Henderson, MD, PhD, designed the study to understand more about Ybt. “One of the reasons we treat UTIs is out of concern that the bacteria will invade other areas and go from being a nuisance to a much more serious infection. Because Ybt seems to be associated with more virulent bacteria, we wanted to understand what it's doing and why it's there,” said Dr. Henderson in the press release.

The results of the new study indicated that Ybt imports copper to ignite biochemical reactions which cause E. coli bacteria to grow and reproduce. Once they have depleted all the copper inside the cell, Ybt will go outside of the cell to get more copper. According to the study, this process is referred to as “nutritional passivation” alluding to “treating or coating metal to make it less reactive.” The results also showed that copper is not the only metal that Ybt exploits. The molecule can also bind to iron and cobalt, among others.

Dr. Henderson, a senior author of the study and an associate professor of medicine at Washington University School of Medicine described the process in the press release, stating, “At the site of infection, this molecule appears to be grabbing onto metals all around it, preventing these metals from reaching toxic levels, but also bringing in controlled amounts of metal ions for nutritional purposes."

The study proved that strains of E. coli that did not possess Ybt molecules containing copper were more conducive to antibiotic treatment and therefore less aggressive. This key finding lays the foundation for future research of developing antibiotics to prevent Ybt from receiving the nutrients that it weaponizes to fortify strains of UTIs. This drug development has the possibility to impact treatment of pneumonia and other illnesses that occur as a result of bacteria with Ybt molecules.  
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