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Susceptibility to polymyxin B in penicillin G-induced Proteus mirabilis L forms and spheroplasts
Abstract:
A polymyxin B-resistant strain of Proteus mirabilis was converted into L forms and spheroplasts in the presence of penicillin G. This treatment caused a 400-fold increase in polymyxin B susceptibility. The acquired susceptibility was in the range of the natural susceptibility reported for susceptible gram-negative bacteria ( approximately 1 mug/ml). The high susceptibility to polymyxin B was lost as soon as the spheroplasts and L forms were allowed to reconvert into the bacillary form in penicillin-free media. This behavior is strong evidence that the natural resistance of Proteus strains to polymyxins is due to the impermeability of the outer cell wall structures to these antibiotic substances.
Insights
Polymyxin B resistance in Proteus mirabilis was overcome by converting bacteria to L forms and spheroplasts. This transformation temporarily increased susceptibility to polymyxin B, indicating the outer cell wall hinders antibiotic entry.
Area of Science:
- Microbiology
- Antibiotic Resistance
- Bacterial Cell Structure
Background:
- Proteus mirabilis exhibits natural resistance to polymyxin B.
- Polymyxins are critical antibiotics for treating multidrug-resistant Gram-negative infections.
Purpose of the Study:
- To investigate the mechanism behind polymyxin B resistance in Proteus mirabilis.
- To determine if altering bacterial cell wall structure affects polymyxin B susceptibility.
Main Methods:
- A polymyxin B-resistant Proteus mirabilis strain was treated with penicillin G to induce L forms and spheroplasts.
- Polymyxin B susceptibility was measured before and after cell wall alteration.
- Reversion to bacillary form was induced in antibiotic-free media to observe susceptibility changes.
Main Results:
- Penicillin G treatment induced a 400-fold increase in polymyxin B susceptibility in Proteus mirabilis.
- Acquired susceptibility levels approached those of naturally susceptible Gram-negative bacteria.
- Susceptibility was lost upon reversion to the normal bacillary form.
Conclusions:
- The outer cell wall of Proteus strains is a primary barrier to polymyxin B.
- Altering cell wall integrity can re-sensitize resistant bacteria to polymyxins.
- This suggests potential strategies for overcoming antibiotic resistance.