Anti-microbial metabolites from a marine bacterium YMA4

Among studies exploring new anti-microbial agents from marine microbial sources, a Gram-negative bacterium YMA4 was isolated. In the agar-plug diffusion assay, YMA4 showed a strong inhibition effect against Staphylococcus epidermidis, Paenibacillus larvae, and Candida albicans, together with a middle inhibition effect against Staphylococcus aureus. Using MALDI IMS [1] and LC MS/MS molecular network analysis [2], we identified the major anti-bacterial metabolites of YMA4 as cyclic-lipodepsipeptide empedopeptin [3,4] together with several new analogues. However, unlike the consistent and significant inhibition effect shown in the antagonistic assay, the inhibition potency of YMA4 extract against C. albicans was somehow unstable, which implies the interaction between YMA4 and C. albicans is too complicated to be explored through the classic bioactivity guided fractionation and isolation approach. Through the genome mining and HPLC PDA profiling analysis, we successfully isolated and identified the unstable anti-fungal metabolites of YMA4 as polyyne analogues. In conclusion, the Gram-negative bacterium YMA4 has a potent anti-microbial effect against not only Gram-positive pathogens, S. aureus, S. epidermidis, and P. larvae but also pathogenic fungus, C. albicans, by utilizing different types of metabolites.

Acknowledgements: This work was supported by grants from the Ministry of Science and Technology, Taiwan, to Y.-L.Y. (MOST 104 – 2320-B-001 – 019-MY2).

Keywords: cyclic-lipodepsipeptide, polyyne, MALDI IMS, molecular networking, genome mining.

References:

[1] Shih CJ, Chen PY, Liaw CC, Lai YM, Yang YL. Bringing microbial interactions to light using imaging mass spectrometry. Nat Prod Rep 2014; 31: 739 – 755.

[2] Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N, Glukhov E, Wodtke A, de Felicio R, Fenner A, Wong WR, Linington RG, Zhang L, Debonsi HM, Gerwick WH, Dorrestein PC. Molecular networking as a dereplication strategy. J Nat Prod 2013; 76: 1686 – 1699.

[3] Konishi M, Sugawara K, Hanada M, Tomita K, Tomatsu K, Miyaki T, Kawaguchi H, Buck RE, More C, Rossomano VZ. Empedopeptin (BMY-28117), a new depsipeptide antibiotic. I. Production, isolation and properties. J Antibiot 1984; 37: 949 – 957.

[4] Sugawara K, Numata K, Konishi M, Kawaguchi H. Empedopeptin (BMY-28117), a new depsipeptide antibiotic. II. Structure determination. J Antibiot 1984; 37: 958 – 964.