The arms race in nature, usually a battle between predator and prey, is one of the most fascinating phenomena in evolutionary biology. But one arms race that isn’t looking too good for humans is the tussle between bacteria and the antibiotics we have to kill pathogens.
And because bacteria can evolve genetic survival tactics rapidly, much faster than we can find new drugs, antibiotic resistance continues to spread.
It’s this genetic evolution of bacteria a team of scientists from Baylor College of Medicine has set its sights on, looking for a drug to slow down the rate of change, giving antibiotics more time to get on top of an infection.
“Most people with bacterial infections get better after completing antibiotic treatment, but there are also many cases in which people decline because the bacteria develop resistance to the antibiotic, which then can no longer kill the bacteria,” said corresponding author Dr Susan M. Rosenberg, professor of molecular and human genetics, biochemistry and molecular biology, and molecular virology and microbiology at Baylor.
In this study, the researchers screened 1,120 existing drugs approved for human use in order to find any that could slow down genetic mutations in E. coli, and prevent its resistance to the second most prescribed antibiotic in the US, ciprofloxican (cipro).
In cultures and mouse models, one drug – dequalinium chloride (DEQ), most commonly used as an topical antiseptic drug – significantly slowed the evolution of the bacteria, in turn making cipro much more effective at fighting infection.
“Given together with cipro, DEQ reduced the development of mutations that confer antibiotic resistance, both in laboratory cultures and in animal models of infection, and bacteria did not develop resistance to DEQ,” said first author Yin Zhai, a postdoctoral associate in the Rosenberg lab. “In addition, we achieved this mutation-slowing effect at low DEQ concentrations, which is promising for patients.”
Evolution-slowing drugs may be just what this arms race needs. In fact, the study suggests that the end goal would be to slow down pathogen evolution to the point that the body’s immune system could do the work and antibiotics might not be required.
The stress response in bacteria in the presence of cipro can see it multiply rapidly, such as at the start of a course of cipro, at the end, or if any doses were missed. This same stress response can fire up the bacteria’s survival skills, working in mutations that protect it from the drug. Interrupting the efficiency of this built-in program is key to maximizing the efficacy of antiobiotics.
Global bacterial antibiotic resistance was responsible for nearly 1.3 million deaths in 2019. It’s expected to climb to up to 10 million deaths annually by 2050.
The research was published in the journal Science Advances.
Source: Baylor College of Medicine
