Tackling Salmonella Persister Cells by Antibiotic-Nisin Combination via Mannitol

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Therapy

Background:

• Bacterial persisters are dormant, non-dividing cells that cause recurrent infections and are resistant to antibiotics.
• Current antibiotic therapies are ineffective against persister cells due to their reduced metabolism and lack of growth.
• Metabolites that 'wake up' persister cells offer a potential strategy to enhance antibiotic efficacy.

Purpose of the Study:

• To investigate the efficacy of mannitol as an adjunct to ampicillin for eliminating Salmonella persister cells.
• To evaluate the combined effect of nisin, ampicillin, and mannitol in eradicating Salmonella persister cells.

Main Methods:

• Salmonella persister cells were generated and characterized for dormancy and reduced metabolism.
• Various carbon sources (glucose, glycerol, mannitol) were tested as adjuncts with ampicillin.
• The combination of nisin, ampicillin, and mannitol was assessed for its ability to eliminate persister cells.
• Flow cytometry was used to confirm the effectiveness of the trio-combination.

Main Results:

• Mannitol combined with ampicillin showed the highest killing effect among single adjuncts.
• The combination of nisin, ampicillin, and mannitol achieved significant elimination (approximately 78%) of Salmonella persister cells.
• Nisin likely facilitated the uptake of the antibiotic-nisin combination by persister cells attempting to metabolize mannitol.

Conclusions:

• The combination of nisin, ampicillin, and mannitol demonstrates significant potential for eradicating Salmonella persister cells.
• This trio-strategy represents a novel approach to combat persistent bacterial infections and overcome antibiotic resistance.