Nosocomial Bacteria Inhibition with Polymyxin B: In Silico Gene Mining and In Vitro Analysis

Area of Science:

• Microbiology
• Biochemistry
• Genomics

Background:

• Multidrug-resistant bacteria pose a major public health threat, necessitating novel therapeutic strategies.
• Cationic non-ribosomal peptides (CNRPs), including polymyxins, are effective against Gram-negative bacteria.
• Limited treatment options exist for infections caused by multidrug-resistant pathogens.

Purpose of the Study:

• To investigate bacterial capacity for biosynthesizing CNRPs, specifically polymyxins.
• To identify bacterial species with robust polymyxin biosynthetic gene clusters.
• To characterize and evaluate the antimicrobial activity of biosynthesized polymyxins.

Main Methods:

• In silico mining of over 11,000 bacterial genomes to identify polymyxin gene clusters.
• Metabolite characterization using High-Performance Liquid Chromatography (HPLC) and MALDI TOF/TOF analysis.
• Antimicrobial activity testing of Polymyxin B (PMB) against nosocomial pathogens.

Main Results:

• Paenibacillus polymyxa was identified with significant polymyxin biosynthetic gene clusters.
• Metabolite yield of 4 mg/L was achieved with a 20-fold increase in specific activity.
• Polymyxin B demonstrated potent activity against Pseudomonas aeruginosa (4 µg/mL), Klebsiella pneumonia (1 µg/mL), and Acinetobacter baumanii (1 µg/mL).

Conclusions:

• Paenibacillus polymyxa possesses a robust capacity for polymyxin biosynthesis.
• Biosynthesized polymyxins exhibit significant antimicrobial activity against critical nosocomial pathogens.
• This study highlights the potential of bacterial-derived CNRPs as a viable alternative to conventional antibiotics.