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[Problems of resistance of the causative agent of melioidosis to antibiotics]

Iu V Antonov, L D Popovtseva, R G Iarulin

    Antibiotiki I Khimioterapiia = Antibiotics and Chemoterapy [Sic]
    |October 1, 1991
    PubMed

    Insights

    Melioidosis pathogen (P. pseudomallei) shows high antibiotic resistance. Mutants were created that were more sensitive to tetracycline due to altered lipopolysaccharide structure.

    Area of Science:

    • Microbiology
    • Bacterial Genetics
    • Drug Resistance

    Background:

    • Melioidosis, a severe infectious disease, is caused by the bacterium Burkholderia pseudomallei.
    • This pathogen exhibits significant intrinsic resistance to various antibiotics, complicating treatment regimens.
    • Understanding the mechanisms of antibiotic resistance in P. pseudomallei is crucial for developing effective therapies.

    Purpose of the Study:

    • To investigate the genetic basis of antibiotic resistance in P. pseudomallei.
    • To isolate and characterize antibiotic-sensitive mutants of P. pseudomallei.
    • To elucidate the structural changes in lipopolysaccharides associated with altered antibiotic sensitivity.

    Main Methods:

    • Chemical mutagenesis of P. pseudomallei using nitrosoguanidine.
    • Isolation and selection of antibiotic-sensitive mutants.
    • Measurement of cell envelope permeability using radiolabeled tetracycline.
    • Analysis of lipopolysaccharide (LPS) composition using gas-liquid chromatography.

    Main Results:

    • Mutagenesis successfully generated P. pseudomallei mutants with increased sensitivity to antibiotics.
    • Mutant strains displayed a 3-fold increase in 3H-tetracycline uptake and a 20-fold increase in tetracycline sensitivity compared to the parent strain.
    • Gas-liquid chromatography revealed significant quantitative and qualitative alterations in the sugar components of the LPS in the sensitive mutants.

    Conclusions:

    • Lipopolysaccharide structure modifications are linked to increased antibiotic permeability and sensitivity in P. pseudomallei.
    • Targeting LPS biosynthesis or structure could be a potential strategy to overcome antibiotic resistance in melioidosis.
    • Further research into P. pseudomallei LPS is warranted for therapeutic development.

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