Synergistic interactions of ruthenium-based carbon monoxide-releasing molecules (CORMs) and antibiotics in their effects on Escherichia coli

Ali, S, Wareham, LK, Poole, RK and McLean, S ORCID: https://orcid.org/0000-0001-8551-4307, 2026. Synergistic interactions of ruthenium-based carbon monoxide-releasing molecules (CORMs) and antibiotics in their effects on Escherichia coli. Microbiology. ISSN 1350-0872 (Forthcoming)

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Abstract

The emergence of antibiotic-resistant pathogenic bacteria poses a major and growing public health risk. Because antibiotics act on specific molecular targets, bacteria may evolve resistance mechanisms that alter or bypass these targets. This work investigated the antimicrobial effects of carbon monoxide-releasing molecules (CORMs) and their potential for co-administration with a variety of commonly used antibiotics against Escherichia coli. CORMs, commonly transition metal carbonyls, release carbon monoxide under certain conditions. Interestingly, CORMs have been shown to exert antimicrobial activity against bacteria both in vitro and in vivo. However, to effectively treat patients with antibiotic-resistant infections, combination therapies involving two or more antimicrobial agents may be a useful approach. Herein, we report the antimicrobial activity of CORM-2 and CORM-3 against E. coli and importantly, that sub-inhibitory concentrations of either compound in combination with antibiotics showed a significant increase in efficacy of the conventional antibiotics as assessed by inhibition of bacterial growth and reduced viability. Furthermore, administration of subinhibitory concentrations of CORMs increased the antimicrobial activity of multiple antibiotics with a range of modes of action when measured by E-tests and microdilution broth assays. The minimal bactericidal concentrations were reduced 2- to 8-fold and 10- to 63-fold for CORM-2 and CORM-3 respectively. Drug interactions between CORMs and antibiotics were also assessed using checkerboard microdilution methods, providing evidence that CORM activity is synergistic with a wide range of conventional antibiotics tested with fractional inhibitory concentration indices (FICi) between 0.31 and 0.45. These findings demonstrate the antibacterial activity of CORMs and their synergy with a range of commonly used antibiotics, opening potential avenues for CORMs to be used as adjuvants to traditional antibiotic treatments.

Item Type:	Journal article
Publication Title:	Microbiology
Creators:	Ali, S., Wareham, L.K., Poole, R.K. and McLean, S.
Publisher:	Microbiology Society
Date:	21 January 2026
ISSN:	1350-0872
Identifiers:	Number Type 2562417 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	23 Jan 2026 16:58
Last Modified:	23 Jan 2026 16:58
URI:	https://irep.ntu.ac.uk/id/eprint/55118

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