The carbon monoxide‐releasing molecule, corm‐3 (ru(co)₃cl(glycinate)), targets respiration and oxidases in campylobacter jejuni, generating hydrogen peroxide

Abstract

SummaryCarbon monoxide (CO) is a classical respiratory inhibitor, but CO-releasing molecules (CO-RMs) have therapeutic value, increasing phagocytosis, and reducing sepsis-induced lethality. CORM-3, Ru(CO) 3 Cl(glycinate), a ruthenium-based carbonyl that liberates CO under physiological conditions, has previously been shown to inhibit bacterial growth and respiration, even at high concentrations of oxygen. Here, we report the effects of CORM-3 on the microaerophilic foodborne pathogen Campylobacter jejuni. Even at CO-RM (i.e., CO) concentrations that exceed dissolved oxygen levels, CORM-3 does not inhibit microaerobic growth. This insensitivity is not due to failure of CORM-3 to penetrate cells, as revealed by assay with extracellular myoglobin and by the ability of CO from externally added CORM-3 to bind intracellular membrane-associated respiratory oxidases. Even at almost 200 lM oxygen, CORM-3 inhibits formate-dependent respiration and leads to generation of hydrogen peroxide. This work shows that CO-RMs have valuable properties as antimicrobial agents; however, growth inhibition does not always accompany inhibition of respiration, even when ambient oxygen concentrations are low.

The Carbon Monoxide Releasing Molecule CORM-2 Attenuates Pseudomonas aeruginosa Biofilm Formation

“…Exposure of planktonic cultures to CORM-3 results in a temporal decrease in oxygen consumption consistent with the hypothesis that interference of CO with the respiratory chain kills P. aeruginosa [18]. CORM-2 inhibits E.coli , Camplyobacter jejuni and P. aeruginosa PAO1 also under anaerobic conditions [19], [30], suggesting that oxygen is not required as the terminal electron acceptor for CORM-2 activity.…”

Interaction of the carbon monoxide-releasing molecule Ru(CO)3Cl(glycinate) (CORM-3) with Salmonella enterica serovar Typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry

“…1), in agreement with other studies that found CORM-3 to be toxic against a variety of bacterial species Desmard et al, 2009Desmard et al, , 2012Nobre et al, 2007;Smith et al, 2011). However, S. Typhimurium seems to be more sensitive than E. coli to this CO-RM (McLean et al, 2013).…”

The Bactericidal Activity of Carbon Monoxide–Releasing Molecules against Helicobacter pylori

“…2B) shows a Soret band at 418 nm with a trough at 433 nm and bands at 535 and 570 nm, with a trough at 585 nm. These features are characteristic of the in vivo formation of carbonmonoxy adducts binding cytochrome b and c , and have been proposed to arise from the ligation of CO to cbb3 -type cytochrome oxidase, so far the sole terminal oxidase cytochrome of H. pylori [24], [25].…”