Isolation and Characterization of Secondary Metabolites Active against Multi-Drug Resistant Staphylococcus aureus

The increasing presence of multi-drug-resistant pathogens (bacteria, parasites and fungi) is one of the major threats to global health reported by the WHO. The challenge against the antimicrobial resistance (AMR) that is occurring worldwide with an average of 500.000 people died every year requires the development of a great number of novel bioactive compounds, which could potentially be used as new drugs. Here, we present the results obtained from the screening of a homemade culture collection of microorganisms, which have been investigated in search for new secondary metabolites active against the methicillin-resistant Staphylococcus aureus (MRSA), one of the pathogens from the WHO global priority list of antibiotic-resistant bacteria. Through the application of an iterative process of inhibition zone-based screening, we could identify on a small portion of the library (approx. 300 strains) a promising number of isolates, which produced an evident inhibition against the multi-drug resistant gram-positive test bacteria. Based on these observations, the active metabolites produced by 12 isolates have been collected from the supernatants of saturated cultures, purified by means of solid-phase extraction columns and HPLC chromatography, and some of the active components have been identified by mass-spectrometry. In addition, when we tested the purified compounds in an in vitro protein synthesis assay driven by a model mRNA, we found three active inhibitors of translation. In summary, we demonstrate that the biologic development pipeline based on bacterial strains isolated from underexplored environmental settings can produce antimicrobial compounds very active against one of the high-priority pathogenic bacteria.