Acquired resistance

Acquired resistance occurs when a particular microorganism obtains the ability to resist the activity of an antimicrobial agent to which it was previously susceptible. This can result from the mutation of genes involved in normal physiological processes and cellular structures, from the acquisition of foreign resistance genes or from a combination of these two mechanisms.

Unlike intrinsic resistance, traits associated with acquired resistance are found only in some strains or subpopulations of each particular bacterial species. Acquired resistance results from successful gene change and/or exchange involving mutation or horizontal gene transfer via transformation, transduction or conjugation.

Vertical gene transfer

A mutation is a spontaneous change in the DNA sequence within the gene that may lead to a change in the trait which it codes for. Any change in a single base pair may lead to a corresponding change in one or more of the amino acids for which it codes, which can then change the enzyme or cell structure, consequently changing the affinity or effective activity of the targeted antimicrobials. In prokaryotic genomes, mutations frequently occur due to base changes caused by exogenous agents, DNA polymerase errors, deletions, insertions and duplications. For prokaryotes, there is a constant rate of spontaneous mutation of about 0.0033 mutations per DNA replication that is relatively uniform for a diverse spectrum of organisms. The mutation rate for individual genes varies significantly among and within the gene.

Horizontal gene transfer

Many of the antibiotic resistance genes are carried on plasmids, transposons or integrons that can act as vectors that transfer these genes to other members of the same bacterial species, as well l as to bacteria in another genus or species.

• Conjugation occurs when there is direct cell-cell contact between two bacteria (which need not be closely related) and transfer of small pieces of DNA called plasmids takes place. This is thought to be the main mechanism of HGT.
• Transformation is a process where parts of DNA are taken up by the bacteria from the external environment. This DNA is normally present in the external environment due to the death and lysis of another bacterium.
• Transduction occurs when bacteria-specific viruses (bacteriophages) transfer DNA between two closely related bacteria.

These genetic mechanisms give to the bacteria some functional capacities that permit them to survive, the main ones are:

• by prevention of the antimicrobial from reaching its target by reducing its ability to penetrate into the cell
• by expulsion of the antimicrobial agents from the cell via general or specific efflux pumps
• by inactivation of antimicrobial agents via modification or degradation
• by modification of the antimicrobial target within the bacteria

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Link to European IC/HH Core Competencies: Area 4. Infection control activities

References:

• Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med. 2006;119(6 Suppl 1):S3-S10.
• McManus MC. Mechanisms of bacterial resistance to antimicrobial agents.Am J Health Syst Pharm. 1997;54:1420 –1433
• Courvalin P. 1996. The garrod Lecture: Evasion of Antibiotic Action by Bacteria. Journal of Antimicrobial Chemotherapy. 37:855-869

FEM PAGE CONTRIBUTORS 2007

Vladimir Prikazsky

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