For all the good antibiotics do for the world, one of the biggest downsides to their use is the way they indiscriminately kill both the ‘good’ and the ‘bad’. A single course of this life-saving medicine can not only destroy disease-causing invaders in the human body; it can also have an “immense” impact on the gut and its resident collection of microbes. This impact can sometimes lead to an overgrowth of certain bacteria or fungi. For instance, women have up to a 30 percent chance of developing a yeast infection after antibiotic treatment.
Scientists at the University of Illinois at Urbana-Champaign are working on a solution. They have discovered a new antibiotic, called lolamicin, that can hone in on gram-negative pathogens while leaving other microbes alone. There’s still a long road ahead before the drug can be tested on humans, but researchers are hopeful it can serve as a blueprint for future antibiotic development.
Gram-negative bacteria are common causes of infections in the bowels, lungs, bladder, and blood, and they are notoriously difficult to kill. Their resistance to current antibiotics is one of the most urgent threats facing global human health today. Broad-spectrum antibiotics can kill both gram-negative and gram-positive bacteria. But scientists say there is a critical need to find medicine that can target gram-negative bacteria specifically, as they’re more likely to be resistant to our current antibiotics. This gives more microbes that are useful to human health a chance of being spared.
A drug like lolamicin could be just the ticket. In laboratory dishes, when lolamicin was pitted against 130 drug-resistant strains of common gram-negative bacteria, like E. coli, K. pneumoniae, and E. cloacae, the medicine killed every single one, succeeding where many other antibiotics failed. In living rodents, lolamicin also successfully treated acute pneumonia and blood infections, all while sparing the gut microbiome.
In fact, scientists found the medicine had “no effect on gram-positive bacteria or on non-pathogenic gram-negative commensal bacteria” that were living in the mice. That’s an exciting discovery given that even a short course of antibiotics can cause a rapid decrease in the diversity of microbe species living in the human gut, and this can persist for months before returning to normal. The health consequences of those changes are not well understood, but they do seem to leave a patient open to secondary infections after using certain antibiotics.
Lolamicin is different. Unlike amoxicillin (a broad-spectrum antibiotic) or clindamycin (a gram-positive-only antibiotic), this new medicine does “not cause any substantial changes” to the gut microbiome of mice in the month or so after treatment. During this time, mice that had been treated with lolamicin were exposed to a bacterial infection, which often develops in the colon following antibiotic usage: Clostridioides difficile. Those mice treated with lolamicin did not develop C. difficile infections at nearly the same rate as those treated with clindamycin or amoxicillin.
Given that the US alone experiences roughly 500,000 C. difficile infections every year, 30,000 of which are fatal, the development of a microbiome-sparing antibiotic could be life-saving. Scientists are now working to refine their work to ensure that pathogens do not become resistant to lolamicin over time.
“The intestinal microbiome is central to maintaining host health, and its perturbation can result in many deleterious effects, including C. difficile infection and beyond,” the authors conclude. “Consequently, pathogen-specific antibiotics such as lolamicin will be critical to minimizing collateral damage to the gut microbiome; this microbiome-sparing effect would make such antibiotics superior for patients compared with antibiotics in current clinical practice.”
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