Structure elucidation and biological activity of antibacterial compound from Micromonospora auratinigra, a soil Actinomycetes

Abstract

Aims: The aim of this study was to isolate and characterize the bioactive compound of Micromonospora auratinigra, HK-10 and its antibacterial inhibitory mechanism.

Methods and results: An oily bioactive compound was extracted from HK-10 (GenBank accession no. JN381554) and found to have promising antibacterial activity. The compound was characterized as 2-methylheptylisonicotinate (1) by (1) H, (13) C NMR and mass spectroscopy. Minimum inhibitory concentration (MIC) of this molecule was tested by micro broth dilution method and was found to be 70, 40, 80, 60, 60 and 50 μg for Staphylococcus aureus, Bacillus subtilis, Proteus vulgaris, Echerichia coli, Pseudomonas aeruginosa and Mycobacterium abscessus respectively. The effects of compound 1 were studied on bacterial membrane structure using scanning electron microscopy. The results indicated a membrane-disrupting mechanism, resulting in the dysfunction of the cytoplasmic membrane structure and cell death of the pathogenic bacterial strains. Kinetics of growth of the test organisms was also analysed and indicated 2-methylheptylisonicotinate 1 as a bactericidal agent. Furthermore, we have studied the binding affinity of 1 towards different membrane proteins of pathogenic bacteria by in silico analysis.

Conclusions: 2-methylheptylisonicotinate was isolated from M. auratinigra, a rare actinobacterial strain possessing antibacterial activity through a membrane-disrupting mechanism, and has MICs similar to standard antibiotic neomycin sulphate. It is the first report about a strain of M. auratinigra, isolated from Indo-Burma biodiversity hotspot of North-east India with new antimicrobial activities. In silico studies have also supported these results performed on various membrane targets of pathogenic bacteria.

Significance and impact of the study: The antibacterial potential of M. auratinigra is reported for the first time. The results indicate the possible use of 2-methylheptylisonicotinate as a source of antibacterial agent against dreaded human pathogens.

Keywords: Micromonospora auratinigra; actinobacteria; antibacterial compound; antibiotic; docking.