Screening Actinomycetes extracts for antimicrobial compounds against methicillin-resistant Staphylococcus aureus and helper-compounds against aminoglycoside-resistant E. coli

Background: Innovative antibiotic discovery strategies are urgently needed to successfully combat infections caused by multi-drug-resistant bacteria. Methods: We employed a direct screening approach to identify compounds with antimicrobial and antimicrobial helper-drug activity against Gram-positive and Gram-negative bacteria. We used this platform in two different strains of methicillin-resistant Staphylococcus aureus (MRSA) and aminoglycoside-resistant strains of Escherichia coli to screen for antimicrobials compounds, which potentiate the activity of aminoglycoside antibiotics. Screening was performed with 75 known microbial products and 880 extracts from Actinomycetes from a collection at the company Naicons. Results: The antibiotics rifamycin O and thermorubin inhibited the growth of neomycin-resistant E. coli in combination with 1/8 MIC of neomycin, suggesting a potential application as adjuvant drugs for neomycin. Additionally, in the Actinomycetes extract screen, one extract with antimicrobial activity and one extract with gentamicin adjuvant activity against gentamicin-resistant E. coli were identified, demonstrating the applicability of the screening approach. Against MRSA, the paramagnetoquinones, the lantibiotic NAI-107 and the spirotetronate NAI-414 showed the most pronounced antimicrobial activity. Difference is susceptibility towards antimicrobials and extracts were observed between the two MRSA strains used for screening. Conclusion: Compounds with antibacterial and helper drug activity were identified using our screening approach. The results demonstrate the importance of strain selection in antimicrobial screening and highlight the potential of natural products as a source of potential new antibacterial and adjuvant therapies against both Gram-positive and Gram-negative bacteria.