The battle against antibiotic-resistant superbugs recently got a boost from positive results in two studies that may lead to the development of new drugs.
The research in both studies concerns the manipulation of the genetic makeup of resistant bacteria in a way that would make them vulnerable to antibiotic treatment. Researchers in Denmark and the West Indies used genomics tools to study the genes of E. coli and Klebsiella pneumoniae, both of which are classified by the World Health Organization as Priority 1 pathogens. E.coli is the cause of both intestinal and urinary tract infections, while K. pneumoniae is an intestinal bacteria often seen in hospital-acquired infections.
In the E. coli study, the inactivation of a single gene made the E. coli bacteria susceptible to an antibiotic and showed the best potential as a helper drug target candidate.
In studying antibiotic resistant strains of K. pneumoniae, scientists identified specific genes that make the bacteria resistant to colistin — a drug used as a last-measure of treatment. They discovered that by switching off one gene they could make the bacteria susceptible to that antibiotic.
While the application of this approach is still a long way from the hospital or physician’s office, its significance is undeniable.
Silvia Munoz-Price, M.D., an epidemiologist and associate professor of medicine in the division of infectious diseases at Froedert Health and the Medical College of Wisconsin, who is also a board member of the Society for Healthcare Epidemiology of America, said, “The possibility of manipulating the bacterial genome to turn off antibiotic-resistant genes is remarkable. If this manipulation is indeed feasible in vivo, then we are facing a paradigm change in the treatment of antibiotic-resistant organisms. This is a very encouraging finding that deserves timely research as it will re-open our currently depleted antibiotic repertoire.”
That guarded optimism is shared by Janet Haas, R.N., the 2017 president-elect of the Association for Professionals in Infection Control. “This technology is in its infancy, but could be very useful. At the moment, the experiment shows proof of principle in retaining sensitivity to colistin, which is a last-line treatment. The authors state that this is theoretically safe for humans, but there have not been trials as yet.
“This approach could be life-saving for patients with totally resistant organisms. It is even more compelling to think about using this new approach to prevent organisms from becoming resistant in the first place, or to help decrease the amount of antibiotics necessary to effect a cure of infection. However, it looks like we have a lot more to learn before this would be used in clinical practice.”
The lead investigator for both studies was Luca Guardabassi, a professor in veterinary clinical and animal sciences at the University of Copenhagen and director of the One Health Center for Zoonoses and Tropical Veterinary Medicine at Ross University.
But more research is needed, according to Guardabassi. In an email, he said, “We are still far away from clinical applications. We developed a high-throughput method to detect drug targets that can restore susceptibility to the currently available antibiotics.”