Self-assembly nanostructured polysulfoniums as antimicrobial potentiator targeted bacterial membrane reversing...

Area of Science:

• Polymer Chemistry
• Microbiology
• Public Health

Background:

• Antimicrobial resistance (AMR) is a growing global threat driven by antimicrobial misuse.
• The declining antibiotic pipeline necessitates novel strategies to combat resistant pathogens.
• Adjuvant therapies offer a promising approach to enhance current antibiotic efficacy.

Purpose of the Study:

• To design and evaluate sulfur-based cationic polymers (polysulfoniums) as antimicrobial adjuvants.
• To investigate the efficacy of polysulfoniums against Gram-positive and Gram-negative bacteria.
• To explore the potential of polysulfoniums in restoring antimicrobial effectiveness.

Main Methods:

• Synthesis of polysulfoniums.
• Determination of minimum inhibitory concentrations (MICs) against various bacterial strains.
• Assessment of bactericidal activity under aerobic and anaerobic conditions.
• Mechanistic studies involving membrane disruption and redox balance.
• In vivo evaluation of polysulfonium-antibiotic combinations.

Main Results:

• Polysulfoniums demonstrated potent activity against Gram-positive and Gram-negative bacteria (MICs of 2 μg/mL).
• Complete bacterial eradication was achieved within 2 hours under both aerobic and anaerobic conditions.
• Polysulfoniums disrupted bacterial outer membranes and redox balance.
• Combination therapy with polysulfoniums (1,10-PS+) and antibiotics (gentamicin, florfenicol, ciprofloxacin) restored antimicrobial effectiveness.
• In vivo studies showed reduced Salmonella colonization with 1,10-PS+ and ciprofloxacin.

Conclusions:

• Polysulfoniums show significant potential as antibacterial potentiators.
• These polymers can restore sensitivity to existing antibiotics, addressing AMR.
• The findings support polysulfoniums as a viable strategy for sustainable clinical applications against resistant infections.