Loading
Life sciences · Journal article
mBio · August 3, 2026
Raises a question worth testing. It does not answer one.
This in vitro experimental evolution study demonstrates that under laboratory conditions, most nonantibiotics do not broadly select for antibiotic resistance in E. coli, but five specific nonantibiotics and three antibiotics repeatedly drove multidrug resistance through upregulation of the AcrAB-TolC efflux pump, regulated by mutations in acrR and lon. The findings are mechanistically informative but represent a first-step hypothesis about real-world risk that requires clinical and microbiome validation.
In vitro experimental evolution with whole-genome sequencing. E. coli laboratory strains (species and strain not specified in abstract). Intervention: Chronic exposure to one of 40 antibiotics or nonantibiotics during in vitro evolution. Compared with: Baseline (unevolved) E. coli strain cross-resistance profile. n = 168.
Five nonantibiotics and three antibiotics emerged as repeated exceptions selecting for broad antibiotic resistance despite exposure to 40 total drugs Most drug-adapted strains did not become multidrug resistant, indicating that inadvertent cross-resistance is rare Whole-genome sequencing of 168 evolved strains revealed that changes in efflux pump regulation converged on two key regulatory genes: acrR and lon
In vitro laboratory model does not capture human microbiome complexity, polymicrobial interactions, or pharmacokinetics
These findings suggest that certain nonantibiotics warrant closer pharmacovigilance for selection of multidrug resistance in the human microbiome, but clinical and translational studies are needed to establish actual risk in patients. The identified molecular mechanism (efflux pump upregulation) may help prioritize which drugs to study further in preclinical and clinical settings.
In vitro experimental evolution study identifying mechanistic routes to resistance but without clinical validation, patient data, or definitive risk quantification in real-world settings.
As stated by the source record.
Quoted from the source exactly as published.
These findings suggest that certain nonantibiotics warrant closer pharmacovigilance for selection of multidrug resistance in the human microbiome, but clinical and translational studies are needed to establish actual risk in patients. The identified molecular mechanism (efflux pump upregulation) may help prioritize which drugs to study further in preclinical and clinical settings.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
ABSTRACT Many medications not prescribed to treat infectious diseases have antibacterial activity at physiologically relevant concentrations, raising the risk that chronic administration of such nonantibiotics may inadvertently select for resistance in the host microbiome. However, how frequently such exposures select for adaptations that impact broad drug resistance, including to antibiotics, remains unclear. Here, we systematically evolved Escherichia coli under exposure to 40 antibiotics and nonantibiotics and profiled the cross-resistance of the drug-adapted strains to 21 antibiotics representing all major classes. Our measurements revealed that most drug-adapted strains did not become multidrug resistant. However, five nonantibiotics and three antibiotics emerged as exceptions and were repeatedly selected for broad antibiotic resistance. Whole-genome sequencing of all 168 evolved strains revealed that changes in the regulation of efflux pumps repeatedly underlay broad drug resistance and converged into two key regulatory genes, acrR and lon. Our work suggests that although inadvertent antibiotic cross-resistance is rare, specific nonantibiotics can still potentially pose a risk for the emergence of multidrug resistance. IMPORTANCE Many medications not typically prescribed to treat infectious diseases have potent antimicrobial activity at physiological concentrations. This anti-bacterial activity raises concern that long-term administration of such nonantibiotics might unintentionally select for multidrug resistance, including resistance to antibiotics. Using Escherichia coli, we show that in most cases, these nonantibiotics do not broadly select for resistance to antibiotics in vitro. However, we identified five nonantibiotics that repeatedly selected for resistance to multiple antibiotics through a shared mechanism of action—upregulation of the multidrug efflux pump AcrAB-TolC. These findings highlight that while the overall risk is low, certain nonantibiotics may still contribute to the emergence of multidrug resistance. Identifying these high-risk drugs can help guide safer prescribing practices and inform strategies to limit the spread of antibiotic resistance.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.