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Which Non-Antibiotic Drugs Show Antibacterial Activity in Lab Studies?

By Freedom251 Team · · 3 min read

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Some medicines developed for conditions other than bacterial infections can inhibit bacteria in laboratory experiments, and studying how they do so may reveal new antimicrobial targets. But the evidence does not show that these drugs treat infections in people. It also raises a research question: adaptation to some non-antibiotics may overlap with resistance to conventional antibiotics.

What counts as a non-antibiotic with antibacterial activity?

Here, “non-antibiotic” means a drug not ordinarily prescribed to treat bacterial infections. The term describes its usual medical purpose; it does not mean the drug cannot affect bacteria. Conversely, inhibiting bacterial growth in a laboratory does not make a medicine a safe or effective antibiotic for patients.

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What did the 2024 Science study find?

Mariana Noto Guillen, Carmen Li, Brittany Rosener, and Amir Mitchell screened 1,280 drugs against laboratory Escherichia coli in defined growth medium. At 10 μM, 176 non-antibiotics and 142 antibiotics met the initial growth-inhibition cutoff. In follow-up experiments with four replicates, 104 non-antibiotics showed significant growth inhibition. These are results from a laboratory screening system, not a clinical trial. Read the study in Science.

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Many drugs had different genetic interaction profiles

The team then examined 186 drugs using 6,709 barcoded knockout strains, representing 3,500 non-essential E. coli genes, and measured more than two million gene–drug interactions. Most non-antibiotics did not group with established antibiotic classes based on their genetic interaction profiles. About half formed separate modules among themselves, which the authors say may point to shared, underused bacterial targets. This suggests avenues for target discovery; it does not establish that the drugs themselves are suitable treatments.

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Transport and efflux affected both groups

Disabling at least one transport system increased bacterial sensitivity to 93% of the antibiotics and 82% of the non-antibiotics in the genetic analysis. Transport and efflux systems can therefore shape susceptibility to both groups, even when their primary toxic effects differ. The authors summarize the finding this way: “Non-antibiotics and antibiotics use divergent toxicity mechanisms in bacteria yet are both impacted by shared efflux systems.”

Could non-antibiotics contribute to antibiotic resistance?

The study evolved E. coli under exposure to three non-antibiotics: streptozotocin, triclabendazole, and sertraline. The adapted bacteria provide laboratory evidence that responses to a non-antibiotic can coincide with changes relevant to antibiotic susceptibility.

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Sertraline-adapted bacteria showed cross-resistance

Sertraline-adapted strains carried mutations in regulators associated with efflux pumps and showed broad cross-resistance across the antibiotic panel tested. This is a result in experimentally adapted bacteria; it does not establish that people taking sertraline develop antibiotic-resistant infections.

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Triclabendazole pointed to a different target

Triclabendazole-adapted strains had mutations in infB, the gene encoding translation initiation factor IF2. Follow-up assays indicated that triclabendazole and two related drugs bind IF2. The finding identifies a possible bacterial target and a laboratory adaptation pathway, not a measured risk in treated people.

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The authors used a well-characterized laboratory E. coli strain as a high-throughput platform and call for further study in human microbiome isolates and in people receiving these medicines. Whether the observed adaptation occurs in treated individuals, and how clinically important it might be, remains unresolved.

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What do drug-combination experiments add?

A separate 2023 Nature Microbiology study tested non-antibiotic medicines alongside antibiotics against Staphylococcus aureus. Across 52 non-antibiotics, it reported 140 synergistic interactions and 105 antagonistic interactions, mainly involving antibiotics. The results show that a non-antibiotic can enhance or weaken an antibiotic’s effect under particular experimental conditions; they do not establish a general rule for drug combinations. Read the combination study in Nature Microbiology.

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One combination, ibuprofen plus gentamicin, was validated against a resistant MRSA clinical isolate in vitro and in a Galleria mellonella infection model. This is preclinical evidence: a result in a dish or an insect model is not an established human treatment. The S. aureus combination experiments and the E. coli screening and evolution experiments also involve different organisms and methods, so their findings should not be treated as directly interchangeable.

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What the evidence does—and does not—support

  • Supported: In the tested laboratory E. coli system, many non-antibiotics inhibited bacterial growth, and their genetic interaction patterns often differed from established antibiotic classes.
  • Supported: Transport systems affected sensitivity to both antibiotics and non-antibiotics, and some laboratory-evolved responses to non-antibiotics coincided with antibiotic cross-resistance.
  • Supported: In tested S. aureus combinations, non-antibiotics could interact with antibiotics in either a synergistic or antagonistic way.
  • Not established: That these medicines can safely or effectively treat bacterial infections in people, that the experimental combinations benefit patients, or that taking the drugs causes a population-level increase in antibiotic resistance.

The results make non-antibiotics useful subjects for studying bacterial targets, transport, and resistance pathways. They do not justify using these medicines to treat an infection or combining them with antibiotics outside medical care.

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antibiotic resistanceantimicrobial resistancebacterial infectionsdrug research

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