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Thursday, March 12, 2009

article : Antibiotic Resistance

Bacterial Resistance to Antibiotics is either:

    1. Intrinsic (inherent) or phenotypic
    2. Acquired via acquisition of foreign resistance genes
    3. Acquired via mutational events in the native genome

Intrinsic Resistance: organism is inherently not susceptible to the antibiotic

Phenotypic Resistance (non-genetic) (e.g., non-growing cells; gram-negative, outer cell membrane)

Genotypic Resistance: Exchange of r-Determinants (Genes that confer resistance to specific antimicrobial agents); Transfer and recombination of resistant mutant genes is possible through normal bacterial genetic exchange mechanisms (conjugation; transduction; transformation)

Plasmids: Multidrug (multiple) resistance is possible; Can cross species barrier and closely related strains may acquire r-determinants

    Plasmid: covalently closed circular extrachromosomal DNA

      Dispensable
      May carry genes for drug resistance; metabolic enzymes; virulence factors (e.g., exotoxins)
      Restricted or broad host range
      Small size (~5 Md) are non-conjugal; Large (20-200 Md) can be conjugal

    Plasmid transfer between cells

      Bacterial conjugation ("sex"):Replication and transfer of the conjugal plasmid via cell-to-cell contact through an F-pilus encoded by tra (transfer) genes
      Transduction: Transferred by phage
      Transformation possible

Transposons (Tn) (plasmid or chromosomal): Genes transferable within a replicon via self-excision; Multidrug resistance is possible; Can cross species barrier

Integrons found on transposons or plasmids; Contains the gene and the site for incorporating resistance genes as cassettes allowing expression of the genes; Multidrug resistance is possible

Selective chromosomal mutations (single drug resistance)

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