Background
The misuse of antibiotics in the last decade led to the quick emergence of antibiotic resistance among pathogenic microorganisms. It has become a serious health problem that motivates researchers to explore new antimicrobial compounds. Micromonospora is one of the most important producers of commercially successful secondary bioactive metabolites, especially antibiotics such as aminoglycosides, enediynes, and oligosaccharides. This study highlights the potential of Micromonospora spp. as a source of novel antibacterial agents against multidrug resistant human enteric pathogens.
Results
The metabolic extract from Micromonospora sp. 65SH showed the lowest MIC against Enterobacter sp. (25 µg/ml) and E. coli (12.5 µg/ml). We performed 16S rRNA gene sequencing to confirm the isolate’s identification at the genus level. Non-targeted metabolomics and molecular LC-QTOF-MS-MS modeling technique were used to identify potential compounds, mechanisms of action and target sites for new antibiotics derived from Micromonospora sp 65SH. The non-targeted metabolomics and molecular modeling of strain 65SH have shown six inhibitors to interfere with the E. coli ATP synthase and possible direct inhibitory effect on the ATP-dependent bacterial topoisomerases. These are: Melibiose, Oligomycin A, Queuine, Heptelidic acid, Diethyl phthalate, and 2'-Deoxyguanosine.
Conclusion
This research on Micromonospora metabolites holds promise for identifying unique compounds, understanding their mechanisms of action, and ultimately developing innovative strategies to target ATP synthase and address various diseases or conditions associated with aberrant energy metabolism. As scientists delve deeper into this relatively unexplored area, the future holds exciting prospects for the discovery and development of Micromonospora-derived ATP synthase inhibitors to combat antibiotic resistance.