Antibiotics reduce ability of immune cells to kill bacteria

Antibiotics can reduce the ability of immune cells to kill bacteria, new research has shown. Further, the changes treatment with antibiotics elicit in the biochemical environment can protect bacterial pathogens in the body.

Previous studies have shown that some antibiotics can damage mitochondria in mice and in human epithelial cells that line the surfaces of the body such as the skin, blood vessels, etc forming a protective barrier between the outside and the inside of the body, for example, from viruses.

Previous studies also showed that bacterial susceptibility to drugs can be affected by small molecules, called metabolites, which are released by cells as intermediates of metabolic reactions. The research team suspected that antibiotic treatment might further alter the infection microenvironment in ways that impact bacteria and immune cells.

To investigate, the team treated mice infected with Escherichia coli bacteria with ciprofloxacin, a common antibiotic. It was administered through the animals’ drinking water at concentrations relative to what a human would receive, and the biochemical changes were quantified. The antibiotic elicited systemic changes in metabolites — not only by influencing the microbiome, but also by acting directly on the mouse tissues.

COUNTERPRODUCTIVE CHANGES

On further investigation, the team determined that metabolites released by mouse cells made E. coli more resistant to ciprofloxacin. Antibiotic exposure also impaired immune function by inhibiting respiratory activity in immune cells: Macrophages treated with ciprofloxacin were less able to engulf and kill E. coli bacteria.

“You generally assume that antibiotics will significantly impact the bacterial cells, and yet here they seem to be triggering responses in mammalian cells,” said senior author James Collins.

“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.”

The study published in the journal Cell Host & Microbe highlights the potential of antibiotics to modulate the immune system, and reveals the importance of the metabolic microenvironment in resolving an infection.

And in the face of growing threat of antibiotic resistance, understanding the myriad impacts of antibiotics is a critical goal for researchers and clinicians formulating better treatments.

“If we have a better understanding of the specific effects that antibiotics can have on different cells, this may help us make decisions about how to better treat infection,” said Jason Yang, a postdoctoral scholar at the Broad Institute and MIT. Translating this findings to human health will require follow-up research. “We need to do additional animal studies under a broader range of conditions and with a broader range of antibiotics, and potentially measure metabolites in human patients undergoing treatment, to see what else might be happening,” said Collins.