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Polycations sensitize enteric bacteria to antibiotics.

M Vaara, T Vaara

Antimicrobial Agents and Chemotherapy

|July 1, 1983

Summary

This summary is machine-generated.

Polymyxin B nonapeptide sensitizes bacteria like Escherichia coli and Salmonella typhimurium to hydrophobic antibiotics. This effect, similar to lysine polymers, enhances antibiotic efficacy against specific bacterial strains.

Related Experiment Videos

Area of Science:

Microbiology
Pharmacology
Bacterial Physiology

Background:

Polymyxin B is a potent antibiotic but its clinical use is limited by toxicity.
Polymyxin B nonapeptide (PMBN) is a derivative lacking the fatty acyl chain and bactericidal activity.
Understanding PMBN's mechanism of sensitizing bacteria to other antibiotics is crucial for novel therapeutic strategies.

Purpose of the Study:

To investigate the ability of Polymyxin B nonapeptide (PMBN) to sensitize Gram-negative bacteria to hydrophobic antibiotics.
To compare the sensitizing effect of PMBN with other polycations, including lysine polymers and natural polyamines.
To determine the concentration-dependent effects of these agents on bacterial susceptibility.

Main Methods:

Treatment of smooth encapsulated Escherichia coli (O18:K1) and Salmonella typhimurium with PMBN and various polycations.
Assessment of bacterial sensitivity to a panel of hydrophobic antibiotics (novobiocin, fusidic acid, erythromycin, clindamycin, nafcillin, cloxacillin) post-treatment.
Evaluation of bactericidal activity and sensitizing effects at different concentrations.

Main Results:

PMBN significantly sensitized both E. coli and S. typhimurium to hydrophobic antibiotics, rendering them as susceptible as deep rough mutants.
A lysine polymer (lysine 20) demonstrated a similar sensitizing effect to PMBN.
Larger lysine polymers and salmine exhibited bactericidal activity at higher concentrations but also sensitized bacteria at sublethal doses. Shorter lysine polymers and other tested agents showed no significant effect.

Conclusions:

Polymyxin B nonapeptide effectively enhances the susceptibility of Gram-negative bacteria to hydrophobic antibiotics.
Polycations, particularly lysine polymers, can modulate bacterial membrane permeability and antibiotic sensitivity.
PMBN represents a promising agent for combination therapy to overcome resistance to hydrophobic antibiotics.