The solution to combating antibiotic resistance—one of the greatest threats to global health—might be right beneath our feet. As bacteria evolve genetic defences that render our existing antibiotics ineffective, microbiologists are urgently seeking new antimicrobial agents.
Elaine Jinfeng Chin, a Postdoctoral Researcher at A*STAR’s Singapore Institute of Food and Biotechnology Innovation (SIFBI), has turned to the natural world for answers, specifically examining bacteria from Singapore's soil.
“Actinobacteria are a diverse group of bacteria known for producing bioactive compounds,” said Chin. These microorganisms are like miniature factories, responsible for about 45 percent of all bioactive compounds derived from microbes. They have also been pivotal in developing treatments for infections, cancer and inflammation. Yet despite their known potential, the actinobacteria indigenous to Singapore's soil are relatively uncharted.
To dig for answers, Chin and colleagues probed these microbial resources by cultivating selected strains from A*STAR’s diverse Natural Product Library under different culture conditions. This method, known as the OSMAC (One Strain Many Compounds) approach, is designed to activate different secondary metabolite gene clusters within the actinobacterial strains by altering their environmental and cultural conditions, said Chin.
The team then tested extracts from those strains against a range of pathogens that cause human diseases. The strains that showed potent antimicrobial activity were then cultivated on a larger scale. Extracts from them were then purified to isolate bioactive components.
Next, the researchers employed high-resolution mass spectrometry and nuclear magnetic resonance to shed light on the chemical structures of these compounds. They identified nine known antimicrobial compounds as well as a novel one—tetronomycin A, which proved effective against both Staphylococcus aureus (SA) and its more formidable variant, methicillin-resistant Staphylococcus aureus (MRSA).
Both SA and MRSA are notorious not only for the severe infections they cause in both healthcare and community settings, but for the resistance they have developed to many antibiotics.
“The discovery of tetronomycin A provides hope for research to expand the repertoire of potential antimicrobial agents,” said Chin, highlighting its potential use in creating compound libraries for further antimicrobial efficacy evaluations.
Currently, the team is focused on deciphering tetronomycin A's mechanism of action and conducting structure-activity relationship studies to explore its viability as a novel antibacterial agent.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Institute of Food and Biotechnology Innovation (SIFBI).
