RT Journal Article SR Electronic(1) A1 Rana, Namrata A1 Jesse, Helen E. A1 Tinajero-Trejo, Mariana A1 Butler, Jonathan A. A1 Tarlit, John D. A1 von und zur Muhlen, Milena L. A1 Nagel, Christoph A1 Schatzschneider, Ulrich A1 Poole, Robert K.YR 2017 T1 A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κ3N)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli JF Microbiology, VO 163 IS 10 SP 1477 OP 1489 DO https://doi.org/10.1099/mic.0.000526 PB Microbiology Society, SN 1465-2080, AB Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ3 N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ3 N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ3 N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ3 N)]Br., UL https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.000526