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Plasmid-mediated sulfanilamide resistance

T Nagate, M Inoue, K Inoue

    Microbiology and Immunology
    |January 1, 1978
    PubMed
    Summary
    This summary is machine-generated.

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    Escherichia coli exhibits two distinct dihydropteroate synthetase (DHPS) enzyme types: a heat-stable, sulfanilamide-sensitive form and a heat-sensitive, sulfanilamide-resistant form. Plasmids influence DHPS activity, potentially conferring drug resistance through altered enzymes or reduced drug permeation.

    Area of Science:

    • Microbiology
    • Molecular Biology
    • Biochemistry

    Background:

    • Dihydropteroate synthetase (DHPS) from Escherichia coli K12 ML1410 is heat-stable and inhibited by sulfanilamides (Sa).
    • Drug resistance plasmids in E. coli can confer altered DHPS activity, leading to sulfanilamide (Sa) resistance.

    Purpose of the Study:

    • To investigate the biochemical mechanisms of sulfanilamide (Sa) resistance in Escherichia coli mediated by drug resistance plasmids.
    • To explore the evolutionary pathways of Sa resistance determinants on plasmids.

    Main Methods:

    • Enzyme activity assays for dihydropteroate synthetase (DHPS) in E. coli strains with and without resistance plasmids.
    • Analysis of DHPS properties (heat stability, Sa sensitivity) in relation to plasmid carriage.
    • Characterization of resistance mechanisms for various plasmid resistance profiles (single, double, triple, quadruple).

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    Main Results:

    • E. coli ML1410 possesses a heat-stable, Sa-sensitive DHPS.
    • Plasmids conferring single or double resistance (Sa, Sa.Tc, Sa.Sm) result in a heat-sensitive, Sa-resistant DHPS, making the cell diploid for DHPS.
    • Triple (Cm.Sm.Sa, Tc.Sm.Sa) and quadruple (Cm.Tc.Sm.Sa) resistance mechanisms likely involve decreased drug permeation rather than altered DHPS.

    Conclusions:

    • Two distinct mechanisms of sulfanilamide (Sa) resistance exist in E. coli, mediated by plasmids: altered DHPS enzyme activity and reduced drug permeation.
    • The presence of different resistance profiles on plasmids suggests an evolutionary process for Sa resistance determinants.