Bacteria synthesize the cellular growth factor putrescine through a number of pathways. One pathway involves the decarboxylation of arginine by arginine decarboxylase to produce agmatine, which is then degraded to putrescine. While important for various cellular processes (e.g., cell division, differentiation, environmental stress responses) in all living organisms, including plants, high levels of this polyamine can be toxic.[1] α-(difluoromethyl)-DL-Arginine (DFMA) is an enzyme-activated, irreversible inhibitor of the arginine decarboxylases of E. coli (Ki = 800 µM), P. aeruginosa, and K. pneumoniae.[2] At 0.01 mM, it has been shown to prevent the osmotic stress-induced increase in arginine decarboxylase activity and putrescine synthesis in oat leaf cells.[3],[4] DFMA can also reduce the growth of T. cruzi in mammalian host cells at a minimal concentration of 10 mM and prevent the growth of C. parvum in a T cell receptor alpha-deficient mouse model when combined with various polyamine analogs.[5],[6]
Reference:
[1]. Gill, S.S., and Tuteja, N. Polyamines and abiotic stress tolerance in plants. Plant Signal. Behav. 5(1), 26-33 (2010).
[2]. Kallio, A., McCann, P.P., and Bey, P. DL-α-(Difluoromethyl)arginine: A potent enzyme-activated irreversible inhibitor of bacterial decarboxylases. Biochemistry 20(11), 3163-3168 (1981).
[3]. Tiburcio, A.F., Kaur-Sawhney, R., and Galston, A.W. Polyamine metabolism and osmotic stress. II. Improvement of oat protoplasts by an inhibitor of arginine decarboxylase. Plant Physiology 82, 375-378 (1986).
[4]. Flores, H.E., and Galston, A.W. Polyamines and plant stress: Activation of putrescine biosynthesis by osmotic shock. Science 217(4566), 1259-1261 (1982).
[5]. Kierszenbaum, F., Wirth, J.J., McCann, P.P., et al. Arginine decarboxylase inhibitors reduce the capacity of Trypanosoma cruzi to infect and multiply in mammalian host cells. Proceedings of the National Academy of Sciences of the United States of America 84(12), 4278-4282 (1987).
[6]. Yarlett, N., Waters, W.R., Harp, J.A., et al. Activities of DL-α-difluoromethylarginine and polyamine analogues against Cryptosporidium parvum infection in a T-cell receptor α-deficient mouse model. Antimicrobial Agents and Chemotherapy 51(4), 1234-1239 (2007).