Anti-ESBL derivatives of marine endophytic Streptomyces xiamenensis GRG 5 (KY457709) against ESBL producing bacteria

The emerging threat of extended spectrum beta lactamase (ESBL) producing Gram negative bacteria still remains an important worldwide concern. Due to insufficient drug choice and treatment failure of existing drugs, novel drugs are needed to combat related infections and bacterial virulence. In this context, the marine Streptomyces xiamenensis GRG 5 (KY457709) was extracted and purified by bioassay guided fractionations and was found to possess excellent anti-bacterial activity against Pseudomonas aeruginosa (MN310553) and Klebsiella pneumoniae (MN368594). The minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) of the fractionated compound were found to be 60 mu g mL(-1). Spectroscopic analyses allowed identifying the chemical components of 2-hydroxy,3,5-di-tetra-butylbenzylidene-amino-indan-2-ol (DTBHAI) in fraction 3. Fluorescence microscopy indicated that the intracellular membrane of ESBL producing bacteria was damaged upon exposure to DTBHAI. Scanning electron microscopy suggested the complete cell lysis and shape modification of the bacterial outer membrane morphology due to DTBHAI. The beta lactamase degradation effect was confirmed by the increased oxidation level in bacteria after treatment with DTBHAI. Furthermore, the hemolytic assay results suggested that compound DTBHAI is biocompatible with human red blood cells. Finally, the molecular interactions between the DTBHAI and ESBL genes were identified by docking and molecular dynamics simulations.

Automated summary

The emerging threat of extended spectrum beta lactamase (ESBL) producing Gram negative bacteria is a major global concern. Marine Streptomyces xiamenensis GRG 5 has been found to possess excellent antibacterial activity against Pseudomonas aeruginosa and Klebsiella pneumoniae. Compound DTBHAI extracted from this strain can damage the intracellular membrane and outer membrane morphology of ESBL producing bacteria, making it a potential treatment option for related infections.