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Antibiotics normally act in concert with an organism’s immune system to eliminate an infection. However, the drugs can have broad side effects, including eliminating “good” bacteria in the course of fighting off a pathogen. Researchers has shown that antibiotics can also reduce the ability of mouse immune cells to kill bacteria, and that changes to the biochemical environment directly elicited by treatment can protect the bacterial pathogen.
Different types of antibiotics can damage mitochondria in mice and in human epithelial cells, and that bacterial susceptibility to drugs can be affected by small molecules, called metabolites, released by cells as intermediates of their metabolic reactions. Antibiotic treatment might further alter the infection microenvironment in ways that impact bacteria and immune cells.
To investigate, the team treated mice infected by Escherichia coli bacteria with a commonly used antibiotic called ciprofloxacin, administered through the animals’ drinking water at concentrations relative to what a human would receive, and quantified the biochemical changes. The researchers found that the antibiotic treatment elicited systemic changes in metabolites-not by influencing the microbiome, but by acting directly on the mouse tissues.
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.
The results highlight the potential of antibiotics to modulate the immune system, and reveal the importance of the metabolic microenvironment in resolving an infection.
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