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[Isolation and characteristics of polymyxin-resistant mutants of Shigella flexneri]
Abstract:
Some characteristics of S. flexneri 2a mutants resistant to various concentrations of polymyxin M were studied. The data indicate that mutations resulting in low (50 microgram/ml) and high (300 microgram/ml) levels of the antibiotic resistance were determined by different genes. Polymyxin resistance led to changed permeability of the outer membrane with respect to detergents and some antibiotics, such as aminoglycosides, penicillins, chloramphenicol and amphotericin B but did not change sensitivity of the strains to some bacteriophages, except phage PI. Mutants resistant to 50 microgram/ml of polymyxin M preserved their ability to induce keratoconjunctivitis in guinea pigs. Part of the strains resistant to 300 microgram/ml of the antibiotic lost this property. No correlation between the polymyxin M resistance level, loss of the pathogenic properties and toxicity of the bacterial cells was found. It was confirmed that though inactivation of endotoxin by polymyxins is associated with their capacity for interaction with lipid A, this component does not participate in development of resistance to these antibiotics.
Insights
Different genes control polymyxin M resistance in Shigella flexneri 2a. This antibiotic resistance alters outer membrane permeability but doesn't affect virulence or toxicity, impacting drug development.
Area of Science:
- Microbiology
- Bacterial genetics
- Drug resistance
Context:
- Shigella flexneri 2a is a significant human pathogen.
- Polymyxins are critical antibiotics for treating infections caused by Gram-negative bacteria.
- Understanding antibiotic resistance mechanisms is crucial for effective treatment strategies.
Purpose:
- To investigate the genetic basis of polymyxin M resistance in S. flexneri 2a.
- To characterize the phenotypic changes associated with polymyxin M resistance.
- To explore the relationship between polymyxin M resistance, virulence, and bacterial cell toxicity.
Summary:
- Mutations conferring low (50 µg/ml) and high (300 µg/ml) levels of polymyxin M resistance in S. flexneri 2a are controlled by distinct genes.
- Polymyxin M resistance alters outer membrane permeability to detergents and certain antibiotics (aminoglycosides, penicillins, chloramphenicol, amphotericin B) but not to most bacteriophages, with the exception of phage PI.
- While low-level resistance mutants retained virulence (keratoconjunctivitis induction), high-level resistance mutants showed a partial loss of this property. No correlation was found between resistance level, virulence loss, and bacterial toxicity. Lipid A interaction is not involved in resistance development.
Impact:
- This study elucidates the genetic and phenotypic consequences of polymyxin M resistance in S. flexneri 2a.
- Findings contribute to understanding antibiotic resistance mechanisms, informing the development of new therapeutic strategies.
- Highlights the complex relationship between antibiotic resistance and bacterial pathogenicity.