Bioprospecting Heavy-Metal Rhizospheres for Novel Therapeutics Against High-Priority Multi-Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii: A Case of Toxic to Treatment

Abstract

This study investigated the antimicrobial potential of rhizospheric microbiota isolated from heavy-metal-contaminated soils against two extremely drug-resistant (XDR) pathogens, Pseudomonas aeruginosa (strain ATCC 27853) and Acinetobacter baumannii (strain ATCC-BAA-1605). Heavy-metal-contaminated rhizospheres were sequentially exposed to ex-situ and in vitro enrichment with heavy metals from battery waste and incubated for 168 h. The surviving microbiota were screened against P. aeruginosa and A. baumannii, and crude extracts of high-performing strains were tested against the pathogens using agar well diffusion assays. The novelty and components of the extracted secondary metabolites from environmentally stressed rhizospheric microorganisms were inferred using ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Results indicated that these secretions inhibited the growth of XDR pathogens (approximately 3.0 × 10⁸ CFU/mL), forming inhibition zones of up to 50 mm. Furthermore, the pathogens were more responsive to exudates from microbiota in environmentally stressed rhizospheres compared to those from organic rhizospheres (control). Heavy-metal-stressed microbiota secrete metabolites that show superior antimicrobial activity and successfully inhibit the growth of XDR pathogens. The UPLC-HRMS analysis indicated the tentative characterisation of the metabolites, particularly Tolyposamine and Gentiatibetine, by the evaluated microbiota, suggesting their relevance as biopharmaceuticals, and could lead to future antibiotic production.