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PreprintCC BYChemRxiv

Antimicrobial Resistance Breakers That Specifically Restore Efficacy of Polymyxins

  • Beth A. Mullan1,2
  • Catherine R. Webley2
  • Prachi Bendale1,2
  • Miguel A. Valvano1
  • Gerd K. Wagner2
  1. 1Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL
  2. 2School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL
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Abstract

Antimicrobial resistance (AMR) is a global threat to human health and prosperity. Antimicrobial resistance breakers (ARBs), molecules that reverse AMR e.g., by blocking enzymes involved in bacterial membrane remodelling, are an attractive solution to restore the efficacy of existing antibiotics. We have identified several hits from in silico screening that restore polymyxin B (PmB) efficacy at concentrations of 250-500 µM in the clinically relevant ESKAPE pathogen Enterobacter bugandensis. The compounds act in tandem with PmB, but not with other antibiotics. They have no significant antibacterial effect themselves and may therefore be regarded as true resistance breakers. Preliminary results suggest that at least two of the three hit compounds may act via covalent bond formation with a target enzyme.

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Cite

BibTeXRIS
BibTeX
@misc{mullan2026antimicrobial,
  title = {{Antimicrobial Resistance Breakers That Specifically Restore Efficacy of Polymyxins}},
  author = {Beth A. Mullan and Catherine R. Webley and Prachi Bendale and Miguel A. Valvano and Gerd K. Wagner},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15009183/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009183/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Antimicrobial Resistance Breakers That Specifically Restore Efficacy of Polymyxins
AU  - Beth A. Mullan
AU  - Catherine R. Webley
AU  - Prachi Bendale
AU  - Miguel A. Valvano
AU  - Gerd K. Wagner
PY  - 2026
DA  - 2026/09/21
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15009183/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009183/v1
AB  - Antimicrobial resistance (AMR) is a global threat to human health and prosperity. Antimicrobial resistance breakers (ARBs), molecules that reverse AMR e.g., by blocking enzymes involved in bacterial membrane remodelling, are an attractive solution to restore the efficacy of existing antibiotics. We have identified several hits from in silico screening that restore polymyxin B (PmB) efficacy at concentrations of 250-500 µM in the clinically relevant ESKAPE pathogen Enterobacter bugandensis. The compounds act in tandem with PmB, but not with other antibiotics. They have no significant antibacterial effect themselves and may therefore be regarded as true resistance breakers. Preliminary results suggest that at least two of the three hit compounds may act via covalent bond formation with a target enzyme.
ER  -