2.2 Spread of antimicrobial resistance in bacteria

Some species of bacteria have intrinsic resistance – an innate ability to resist the action of an antimicrobial which can lead to treatment failure. Resistance can also be acquired. It can develop by mutation, with the newly resistant bacterial clone expanding and spreading under evolutionary pressure from the presence of the antibiotic. However, the main healthcare concern is acquired resistance through horizontal transfer of resistance genes mainly carried by mobile genetic elements, in particular plasmids.

Activity 6 Plasmids

Timing: Allow 5 minutes

From your study of the Introducing antimicrobial resistance module what can you remember about the role plasmids play in the spread of antimicrobial resistance? Make notes in the text box provided.

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Discussion

  • Plasmids are mobile genetic elements easily transmitted between bacteria, including between different strains and species.
  • Plasmids can readily acquire multiple resistance genes which can quickly lead to MDR transmissible strains, making them important in the spread of resistance.
  • Plasmid acquisition, unlike the accrual of multiple mutations, confers immediate high-level resistance to one or often, multiple, antimicrobials and threatens the ability to treat severe infections.
  • Antimicrobial use provides selection pressure on bacteria to retain their plasmids.

Resistance can be shuffled between chromosomal and plasmid DNA on small mobile genetic elements, facilitating recombination and promoting the rapid evolution of new resistant forms. Resistance genes can remain on the plasmid or be integrated into the chromosome; chromosomal mutations can also find their way onto plasmids. This, coupled with horizontal gene transfer which can so easily lead to MDR strains, is the main cause of antimicrobial resistance spreading through Gram-negative bacterial populations – including between different species. Transmissible resistance mediated by plasmids and other mobile genetic elements (such as transposons or insertion sequences), is therefore of huge global concern in both human and animal health.

The current greatest AMR threat to modern medicine is from plasmids with a carbapenemase gene plus resistance to multiple antimicrobials. In any of the three organisms in the WHO ‘critical’ R&D category, carbapenem-resistance leads to infections that can only be treated with combinations of drugs or toxic ‘third line’ antimicrobials, for example, colistin. These plasmids can lead to untreatable infections, hence the high priority placed on these pathogen-AMR combinations.

2 Antimicrobial resistance

3 Pathogen-AMR combinations