Lecture DetailsEdit

Priscilla Johanesen; Week 12 MED1011

Lecture ContentEdit

Mechanisms of resistance to antibodies are innate, alteration of target site, access to target site, altered uptake, modification or destruciton of antimicrobial. Some bacteria have innate resistance to an antibiotic (penicillin and mycobacterium TB). Alteration and access to target site can be modified by random chromosomal mutation (changing base sequences in DNA resulting in a permanent, heritable change in genetic material). Horizontal gene transfer can occur using plasmids, transposons or pathogenicity islands.

Plasmids are DNA molecules that exist separate to the host chromosome, they are circular, self replicating and are a double stranded DNA molecule. They encode control of their replication, resistance mechanisms (antibiotics and heavy metals), virulence genes (toxin production, inhibition of phagocytosis, secretion systems), metabolic enzymes, production of antimicrobials and mobility factors. Resistance plasmids affect uptake or inactivate drug. Some plasmids are transmissible between bacterial cells (conjugative plasmids).

Transposons are 'jumping genes', mobile genetic elements that transfer DNA within the cell. Can be plasmid-plasmid or plasmid-chromosome. Can have insertion sequences (150-1500bp, transposase gene) or composite transposons (transposase gene bound by inverted repeat sequences, has a central region of extra genes, antibiotic resistance, virulence factors. Plasmid-mediated resistance on a transposon allows for spread of resistance.

Bacterial antibiotic resistance is due to fast growth rates, use of antibiotics, spontaneous mutations and selection, presence of plasmid-mediated and transposable antibiotic resistance genes

Restrict antibiotic use, restrict agriculture use of antibiotics, use prescription only if needed. Develop new antimicrobials, designer antibiotics, search for natural compounds. Drug design can take 12-25 years and cost hundreds of millions.


Mims 33 479-503Edit