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This page has background information (including links) for antibiotic resistance.

Useful Information about Antibiotic Resistance

Classification of Standard Biological Parts Related to Antibiotic Resistance

In synthetic biology we dissect out functional elements from natural genomes or synthesize artificial elements of our own design. We then devise ways to combine these elements in a living cell so as to confer on it desired characteristics. As indicated above, cells have evolved the property of antibiotic resistance using at least five different mechanisms:

1. chemical modification of the antibiotic,
2. blockage of the channels or pores that allow the antibiotic molecules to enter the cell,
3. active transport of the antibiotics out of the cell,
4. replacement of the antibiotic's normal target with an unaffected component, and
5. creating or activating a pathway that detours around antibiotic-induced blockage.

The devices/systems cells use to produce such mechanisms vary considerably. In the first case, a single enzyme can suffice to destroy antibiotic molecules. Thus that kind of resistance can be engineered into a cell merely by inserting the coding sequence for such an enzyme (assuming it consists of only one kind of polypeptide chain). Most of the antibiotic-resistance parts in the Registry use this mechanism. Tetracycline resistance -- very familiar to synthetic biologists -- works by the third mechanism listed above. A membrane-channel protein (TetA) actively pumps out the antibiotic molecules. This, however, depends upon a control mechanism. The channel protein's coding sequence is repressed in the absence of the drug. A repressor protein (TetR) binds to a specific promoter upsteam of the TetC gene and keeps it shut off until the cell encounters tetracycline. The drug acts as an inducer by binding TetR and causing it to dissociate from the promoter, thereby turning on the gene for the efflux pump. The other antibiotic-resistance mechanisms similarly depend upon specific genes or combinations of genes to neutralize the effects of the drug.

The complexity of many antibiotic resistance mechanisms complicates classification of the genetic elements that make up the parts of a multi-component system. Thus, for tetracycline, the Registry has the genes for the efflux pump, the repressor, and the promoter. These can be used separately, and in the case of the repressor/promoter pair are mostly used as switching elements in genetic circuits that have nothing to do with antibiotic resistance. The pump gene can also be decoupled from its natural repressor/promoter combination and put under regulatory control of other elements. Thus classification must deal with two different types of component. We call the first type "key antibiotic-resistance parts," and the second "supplemental antibiotic-resistance parts."

Links

General References, Mechanisms, etc.

http://www.infectionacademy.org/slides/singapore2006/08-Antibiotics-and-resistance-Goossens.ppt

Aminoglycoside Resistance

This category includes kanamycin, streptomycin, gentamycin, neomycin, tobramycin, amikacin...

http://www.antibioresistance.be/aminoglycosides.html

http://openwetware.org/wiki/Kanamycin

Tetracycline Resistance

This category includes three different resistance mechanisms. Related antibiotics are tetracycline, chlortetracycline, doxycycline, minocycline, oxytetracycline, spectinomycin. Note that the TetR gene encodes a very popular repressor that is frequently used in synthetic biology simply as a single control element in cells that do not express tetracycline resistance. [Check this.]

http://www.antibioresistance.be/Tetracycline/Menu_Tet.html

http://openwetware.org/wiki/Tetracycline

http://cmr.asm.org/cgi/content/abstract/5/4/387