Assessing the antimetabolite activity of modified vitamin B12 analogues against Lactobacillus delbrueckii and Listeriamonocytogenes

Abstract

Developing novel strategies against foodborne pathogens, like Listeria monocytogenes, is crucial due to their growing resistance to current hurdles and disinfection protocols. Disruption of the cobalamin biosynthesis pathway revealed the importance of vitamin B12 (B12) in L. monocytogenes tolerance to cold and copper stress, suggesting that B12 analogues have potential as hurdles against it on food. In 2021, 10-Br-methyl cobalamin (10-Br-MeCbl) was introduced as an L. monocytogenes antimetabolite. Herein, we re-evaluated 10-Br-MeCbl and tested seven related B12 analogues against six L. monocytogenes strains and a B12 auxotrophic Lactobacillus delbrueckii strain. No analogue, including 10-Br-MeCbl, was inhibitory to L. monocytogenes. In contrast, 10-Br-MeCbl, 10-Br-CNCbl, 10-Br-PhCbl, and 10-Br-CNCbl-c-lactam inhibited L. delbrueckii growth (13–27%) at concentrations 50-folds higher than B12. This inhibitory activity was lost under conditions of B12 abundance, indicating competitive inhibition. The activity of phenylcobalamin-c-lactam against L. delbrueckii differed compared to a previous study, emphasizing that the antimicrobial activity of B12 derivatives is not universal and must be examined for each species under the application conditions. Overall, while this study illustrates the potential of B12 antimetabolites as antimicrobials, it also demonstrates that other classes of B12 antimetabolites and/or improved strategies are required for tackling pathogens like L. monocytogenes.