Editors' ChoiceCellular Metabolism

Antibiotics directly affect host cell metabolism

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Sci. Signal.  09 Jan 2018:
Vol. 11, Issue 512, eaas9172
DOI: 10.1126/scisignal.aas9172

Antibiotic treatment alters host cell metabolism in a manner that affects both the efficacy of the drug and the immune response to infection.

In addition to causing unwanted side effects, such as nausea, hearing loss, and tendonitis, antibiotics can alter immune responses and interfere with mitochondrial function. Yang et al. report that antibiotics can also elicit changes in host metabolism that may reduce the efficacy of the drug and interfere with the function of immune cells. The authors performed metabolomic profiling of the peritoneum, lung, and plasma from untreated control mice, mice treated with the antibiotic ciprofloxacin, mice infected intraperitoneally with Escherichia coli, and mice that were both infected and treated with ciprofloxacin. Ciprofloxacin treatment in the absence of infection changed the metabolite profiles of all three tissues compared with those of control samples, but intraperitoneal infection elicited metabolite changes only in the peritoneal tissue. Likewise, some of the metabolite changes detected in the peritoneal tissue of infected mice depended on whether the animals were treated with ciprofloxacin. For example, antibiotic treatment alone mildly increased the concentration of adenosine monophosphate (AMP) in the peritoneum, and infection reduced the concentration of AMP in the peritoneum; however, the combination of infection and antibiotic treatment increased the concentration of AMP in the peritoneum. AMP and other metabolites that were increased in abundance in response to ciprofloxacin treatment increased the concentration of ciprofloxacin that was required to kill E. coli in vitro, suggesting that some of these metabolite changes may reduce the efficacy of the antibiotic in vivo. Ciprofloxacin treatment alone reduced the abundance of central metabolic intermediates in the peritoneum and reduced the respiratory capacity and phagocytic ability of mouse macrophages in culture, consistent with previous reports that antibiotics can interfere with mitochondrial function. However, AMP enhanced the ability of mouse macrophages to engulf and kill bacteria in culture. Although antibiotics are thought to alter host metabolites primarily through their effect on the gut flora, antibiotic treatment elicited metabolite changes in germ-free mice similar to those in colonized mice. These findings illustrate that antibiotics can alter host metabolites by acting directly on host cells and that these changes can affect both the efficacy of the antibiotic and the immune response to infection.

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