Antibiotic Resistance Plasmids in Bacteria

Antibiotic resistance plasmids are bacterial extrachromosomal elements that carry genes conferring resistance to one or more antibiotics. They are notorious for their ability to transfer conjugatively between bacterial species and are significantly involved in the emergence and dissemination of multiple drug resistance.

Keywords: conjugative transposon; horizontal transfer; insertion sequence; integron; plasmid; transposon

Figure 1. The generation of cell-to-cell contact involved in conjugation. (a) An Escherichia coli cell with its plasmid-encoded pilus structure binding to the recipient (plasmid-free) cell and retracting in order to generate direct contact between the two cells. (b) An Enterococcus faecalis donor cell undergoing a plasmid-encoded mating response to a peptide sex pheromone secreted by a recipient cell. The donors synthesize ‘aggregation substance’ that coats the surface and facilitates adherence to recipients upon random collision. Once a copy of the plasmid is acquired, the resulting transconjugant cell shuts down or masks the endogenous pheromone and becomes a potential donor. Interestingly, transconjugants continue to produce other peptide pheromones able to induce a mating response by donors carrying different families of conjugative plasmids. A plasmid-free strain can actually make up to six different pheromones, and probably many more.
Figure 2. Diagram of the erythromycin-resistance transposon Tn917 originally identified in Enterococcus faecalis. The element is a little over 5000 bp long and is bounded by 38-bp inverted repeats (LR, left repeat; RR, right repeat) indicated by the short arrows at the left and right ends. IR (internal repeat) is also a 38-bp repeat which conceivably could work together with RR to move part of the element without the erythromycin resistance gene erm, although this has not actually been demonstrated. tnpA encodes the transposase and tnpR encodes a ‘resolvase’ that acts subsequent to the transposase in ‘resolving’ a cointegrate structure that represents an intermediate in the transposition process. The resistance determinant of Tn917 is inducible, in that a subinhibitory concentration of erythromycin greatly enhances the level of the erm product by an increase in transcription. This can also have an effect downstream by increasing expression of the transposition genes, which can lead to an increase in the frequency of movement of the element.
Figure 3. Structure of an integron. The arrows indicate the relative orientation of the various components. P is the promoter that fires backwards from a site within the 5¢ end of the integrase determinant intI. (intI has its own promoter (the circle at the beginning of the arrow) upstream.) attI is the site where new cassettes enter and become part of the integron. Cassettes move by excision via a ‘loop-out’ involving flanking recombination sequences (i.e. 59-base element (59-be) sequences). The nonreplicating circular element containing one 59-be then enters at the attI sequence. Expression is greatest at the head of the line because it is closest to the promoter P; and exposure to a given antibiotic will select for movement of the appropriate cassette to this position.
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 References
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 Further Reading
    Amabile-Cuevas CF (2003) New antibiotics and new resistance. American Scientist 91: 138–149.
    Clewell DB, Francia MV, Flannagan SE and An FY (2002) Enterococcal plasmid transfer: sex pheromones, transfer origins, relaxases and the Staphylococcus aureus issue. Plasmid 48: 193–201.
    book Levy SB (1992) The Antibiotic Paradox: How Miracle Drugs are Destroying the Miracle. New York: Plenum Press.
    Rowe-Magnus DA and Mazel D (2002) The role of integrons in antibiotic gene capture. International Journal of Medical Microbiology 292: 115–125.
    Salyers AA and Amabile-Cuevas CF (1997) Why are antibiotic resistance genes so resistant to elimination? Antimicrobial Agents and Chemotherapy 41: 2321–2325.
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Clewell, Don B(May 2005) Antibiotic Resistance Plasmids in Bacteria. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003851]