As more strains of bacteria become resistant to antibiotics, scientists are warning that we could soon return to the "dark ages of medicine," where our drugs are ineffective against even the most basic of infections. While investigating the side effects of antibiotics and how bacteria can develop resistance to them, researchers from MIT and Harvard have found that the drugs can actually work against the body, weakening the immune system's ability to fight off the bugs.
To prevent the possible "superbug" doomsday scenario, teams of scientists are developing new treatments that don't require drugs, such as antimicrobial materials, lights and predatory bacteria. But antibiotics will still play an important part in future treatments, as researchers discover new classes of them or supercharge old ones. And in that vein, it pays to have a better understanding of just what antibiotics are doing to the body.
The new study, conducted by researchers at Harvard, MIT, the Wyss Institute for Biologically Inspired Engineering and the Broad Institute, aimed to investigate the ways in which antibiotics affected the body, and how those effects in turn impacted on both the invading bacteria and the host's immune cells. And the changes weren't always for the better.
"Antibiotics interact with cells, particularly immune cells, in ways we didn't expect," says Jason Yang, co-first author of the study. "And the biochemical context, altered by antibiotics and cells in the surrounding tissue, matters when you're trying to predict how a drug might work in different people or in different infections."
The researchers infected mice with E. coli bacteria, and then treated them with a common antibiotic called ciprofloxacin. In doing so, they found that the drug directly affected the tissues of the mice, which in turn changed the metabolites those cells released during the process of metabolism. And these changes were counterproductive, with the metabolites actually working to make the E. coli more resistant to the antibiotic. At the same time, the drugs can make the immune system less effective overall: Immune cells called macrophages were found to be less effective at fighting off infection, because the antibiotic choked out their respiration.
"You generally assume that antibiotics will significantly impact the bacterial cells, and yet here they seem to be triggering responses in mammalian cells," says James Collins, senior author of the study. "The drugs are producing changes that are actually counterproductive to the treatment effort. They reduce the bacterial susceptibility to antibiotics, and the drugs themselves reduce the functional benefit of the immune cells."
While it sure doesn't sound like good news, the researchers say that it's helpful to improve our understanding of what antibiotics are doing to the immune system. Next up, the researchers plan to conduct more detailed animal studies using other antibiotics, and possibly study the metabolites in human patients that are already being treated with antibiotics to see how well the findings may translate across.
The research was published in the journal Cell Host & Microbe.
Source: Broad Institute
