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Updated: Jan 24, 2026

Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
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Second-Generation Tryptamine Derivatives Potently Sensitize Colistin Resistant Bacteria to Colistin

Bradley M Minrovic1, Veronica B Hubble1, William T Barker1

  • 1Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.

ACS Medicinal Chemistry Letters
|May 18, 2019
PubMed

Insights

A novel colistin-adjuvant combination effectively combats antibiotic-resistant Gram-negative bacteria. This adjuvant significantly boosts colistin efficacy against resistant strains, restoring treatment options.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Antibiotic resistance, particularly to polymyxin colistin, is a growing global health threat.
  • Emergence of plasmid-borne colistin resistance genes (mcr 1-8) compromises last-resort antibiotic efficacy.
  • Multidrug-resistant Gram-negative bacterial infections necessitate novel therapeutic strategies.

Purpose of the Study:

  • To investigate a colistin-adjuvant combination therapy for combating colistin-resistant bacteria.
  • To evaluate the efficacy of a lead adjuvant in restoring colistin's effectiveness.

Main Methods:

  • Testing a lead adjuvant at 5 μM in combination with colistin.
  • Assessing adjuvant efficacy against bacteria with plasmid-borne (mcr-1) and chromosomal colistin resistance.
  • Determining the fold-increase in colistin efficacy and minimum inhibitory concentration (MIC) reduction.

Main Results:

  • The lead adjuvant, non-toxic alone, significantly enhanced colistin efficacy.
  • A 32-fold increase in colistin efficacy was observed against mcr-1 harboring bacteria.
  • A 1024-fold increase in colistin efficacy was achieved against chromosomally resistant bacteria.
  • Combinations reduced colistin MIC to clinically relevant levels (≤2 μg/mL).

Conclusions:

  • Colistin-adjuvant combination therapy presents a promising strategy against colistin-resistant Gram-negative pathogens.
  • This approach can restore the clinical utility of colistin for treating challenging infections.
  • Further research into adjuvant-based therapies is warranted to address the antibiotic resistance crisis.

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