Investigators from the University of Colorado Boulder have developed a strategy to fight antibiotic-resistant E coli using genetic disruption.
Much of the effort to find new ways to fight the growing number of antibiotic-resistant bacteria has focused on the need for novel antibiotics; however, in a new study, University of Colorado Boulder investigators found a new approach using genome editing.
The World Health Organization (WHO) calls antibiotic resistance one of the greatest threats to global health, food security, and development. Although bacterial pathogens naturally develop resistance to antibiotics, WHO officials say that the misuse of antibiotics in medical and agricultural applications is speeding up the process. As a result, infections from so-called superbugs are leading to longer hospital stays, higher medical costs, and increased mortality. In the United States, the problem leads to 2 million antibiotic-resistant infections and 23,000 deaths each year, according to estimates from the US Centers for Disease Control and Prevention (CDC).
In 2017, WHO published a global priority list of 12 antibiotic-resistant bacteria. Although Escherichia coli is not one of the “dirty dozen”, this pathogen can cause dangerous illnesses such as intestinal infections, urinary tract infections, respiratory illness, and pneumonia. The growing problem of antibiotic-resistant E coli— including forms of the bacteria with resistance to the last-resort antibiotic colistin—has prompted research into new antibiotics, antibiotic combinations, and alternative strategies to fight once easy-to-treat infections.
In the new study, published in the journal Communications Biology, a team of investigators detailed an experimental new approach to fighting E coli using no antibiotic agents. Instead, the new strategy involved the use of genetic disruption in what they call the "Controlled Hindrance of Adaptation of OrganismS (CHAOS)" approach. This new E coli-fighting tactic uses CRISPR DNA to systematically perturb gene expression in the bacteria. According to the authors, their approach allows them to alter multiple gene expressions within the bacteria cells to stunt its central processes and thwart its ability to evolve defenses.
“We now have a way to cut off the evolutionary pathways of some of the nastiest bugs and potentially prevent future bugs from emerging at all,” said lead author Peter Otoupal, PhD, in a recent press release. Early research by the team focused on 1 gene at a time, but the bacteria were adaptable and survived. “We saw that when we tweaked multiple gene expressions at the same time—even genes that would seemingly help the bacteria survive—the bacteria’s fitness dropped dramatically.”
By launching multiple genetic attacks, the investigators found that Carbapenem-resistant E coli became more susceptible to existing antibiotics. Their findings, they say, suggest a new therapeutic strategy for restricting the evolution of antibiotic resistance, though bringing this research from the lab to the patients will take a commitment of time and research. In an interview with Contagion®, Dr. Otoupal noted that although the cost of a treatment based on this research would likely be significant, he envisions it 1 day being used alongside a last-resort antibiotic.
“The problem that I see is that there hasn’t really been a focus on trying to come up with new strategies to try to restrict the evolution of antibiotic resistance,” said Dr. Otoupal, noting that some drug makers have also ceased their research and development on new antibiotics. “Both are very much in need.”