The Incredible Potential of Cave Actinobacteria in Finding New Antimicrobials and Bioactive Compounds

Antimicrobial resistance is a growing threat that is going to be a leading cause of mortalities in the near future. In the fight against AMR, actinobacteria are historically the leading producers of antibiotics and other bioactive compounds. However, the recurrent isolation of previously discovered compounds from traditional soil actinobacteria has somewhat lessened the impact of actinobacteria. Actinobacteria from underexplored habitats such as caves still possess treasures of wonderful compounds that can be of incredible potential for the discovery of new antimicrobials. Their adaptation to extreme, nutrient-limited cave environments often drives the evolution of unique biosynthetic pathways and cryptic gene expression. In this review, we have discussed some of the recent hallmarks of actinobacteria studies conducted on caves, ranging from their diversity in caves to their metabolomic potential, with the actual isolation of a variety of bioactive compounds. We highlighted the remarkable microbial diversity within cave ecosystems, where actinobacteria often dominate and exhibit potential for producing novel antimicrobial, anticancer, and agro-active metabolites. By integrating genomics, metabolomics, tandem mass spectrometry-based molecular networking, WGS, and bioinformatics pipelines, researchers can now predict, prioritize, and characterize novel compounds more efficiently than ever before. Cave actinobacteria are invaluable and largely untapped reservoir for next-generation antibiotics and drug discovery.