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Smarter Screening to Predict Antibiotic Success Before Animal Testing

At a Glance

Researchers at Colorado State University have developed a new way to predict how well antibacterial drugs will work in the body before they reach animal testing. The method links lab-based results to real-world effectiveness, helping scientists choose the most promising drug candidates earlier. It is already used across multiple research programs, including NIH-funded projects and industry collaborations. This approach improves decision-making in drug development for serious infections like tuberculosis and other high-risk bacterial diseases.

Background

Bacterial infections such as tuberculosis, melioidosis, and tularemia remain major global health threats, especially with the rise of multidrug-resistant strains. Traditional drug discovery methods rely heavily on minimal inhibitory concentration (MIC) data, which often fails to predict how a drug will perform in living systems. This gap leads to wasted time and resources advancing ineffective compounds. A more reliable way to connect in vitro testing with in vivo outcomes is critical for accelerating the development of effective treatments.

Overview

This technology introduces a structured framework for evaluating the relationship between in vitro activity and in vivo efficacy of antibacterial compounds. Instead of relying solely on MIC values, the method incorporates additional biological and pharmacological factors to better predict how compounds will perform in animal infection models. By doing so, it enables researchers to prioritize drug candidates with a higher likelihood of success earlier in the development pipeline.

The approach has been applied across at least five drug discovery programs and has supported thousands of compound evaluations. It is particularly useful for identifying small molecule inhibitors targeting bacterial cell division—an underexplored but promising therapeutic pathway. These compounds have shown strong antibacterial activity with low toxicity, and the method helps confirm which candidates are worth advancing to costly and time-intensive in vivo studies.

Fig. 1. Epetraborole activity in an ex vivo infection model. Epetraborole (EBO) was tested against B. pseudomallei strain 1026b, both alone and in combination with ceftazidime (CAZ; 4 µg/mL). Ceftazidime alone was included as a control. Bacterial growth decreased as EBO concentration increased (0.25–8 µg/mL), with the combination treatment showing consistently strong inhibition across all tested concentrations. All combination doses (0.5–8 µg/mL) significantly reduced bacterial burden compared to untreated controls, with no significant differences observed between doses. Statistical comparisons were performed using ANOVA.
Fig. 2. Effect of delayed treatment with epetraborole in a B. pseudomallei infection model. (A) Timeline of the delayed dosing regimen used in the animal study. (B–C) Bacterial burden in the lung (B) and spleen (C) following treatment with epetraborole (EBO) and ceftazidime (CAZ), administered subcutaneously (SC) or intraperitoneally (IP), either alone or in combination. Each point represents an individual animal. The dotted line indicates the limit of detection.

Benefits

  • Improves prediction of in vivo drug efficacy beyond standard MIC measurements
  • Accelerates identification of high-potential lead compounds
  • Reduces time and cost associated with ineffective candidates
  • Applicable across diverse antibacterial drug discovery programs
  • Supports development of treatments for drug-resistant infections

Applications

  • Pharmaceutical drug discovery pipelines
  • Screening of antibacterial compound libraries
  • Development of therapies for tuberculosis and other serious infections
  • Optimization of combination drug therapies
  • Government and industry-funded infectious disease research programs

Publications

Cummings, JE et al (2023). Epetraborole, a leucyl-tRNAsynthetase inhibitor, demonstrates murine efficacy, enhancing the in vivo activity of ceftazidime against Burkholderia pseudomallei, the causative agent ofmelioidosis. PLoS Negl Trop Dis. https://doi.org/10.1371/journal.pntd.0011795

Cummings, JE et al (2021). TPR1, a novel rifampicin derivative, demonstrates efficacy alone and incombination with doxycycline against the NIAID Category A priority pathogen Francisella tularensis. JAC Antimicrob Resist. doi:10.1093/jacamr/dlab058

C Neckles, et al. (2017) Rationalizing the Binding Kinetics for the Inhibition of the Burkholderia pseudomallei FabI1 Enoyl-ACP Reductase. Biochemistry

S E Knudson, et al. (2015) Cell division inhibitors with efficacy equivalent to isoniazid in the acute murine Mycobacterium tuberculosis infection model. The Journal of antimicrobial chemotherapy 

SE Knudson, et al. (2014) In vitro-in vivo activity relationship of substituted benzimidazole cell division inhibitors with activity against Mycobacterium tuberculosis. Tuberculosis (Edinburgh, Scotland)

Last Updated: May 2026
Circular diagram of the drug discovery process with icons for lab research, analysis, evaluation, and clinical application connected by arrows.
Opportunity

Available for Licensing
TRL: 4

IP Status

US Patent 10287617

Inventors

​Susan E Knudson
Richard A Slayden

Reference Number
14-026
Licensing Manager

Steve Foster
Steve.Foster@colostate.edu
970-491-7100

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