Regulation of antibiotic resistance in bacteria: the chloramphenicol acetyltransferase system.
The evaluations of antibiotic resistance has been a subject of interest to workers in several disciplines. Our current understanding of the molecular biology of plasmids, phages, and transposable elements provides a basis for appreciating the range of mechanisms likely to be involved in the horizontal spread of resistance determinants through microbial ecosystems. Rather less can be imagined with confidence about the origins of the genes or the constraints and selection pressures operating at the level of protein structure. The CAT system illustrates the extent of variation possible for an accessory gene product which is required infrequently and which is encoded by multicopy and promiscuous vectors which can cross taxonomic boundaries. Still less is known with certainty about the evolution of genetic control of the expression of antibiotic resistance. While there are sound reasons for looking in detail at prokaryotic antibiotic-producing organisms such as Streptomyces to find the progenitors of present resistance mechanisms (44, 45), it seems likely that controls of expression have been acquired during the "passage" of selectable markers through more distant bacterial genera. The CAT system is illustrative of the variety we may expect to find in control strategies used by microbial systems generally. It might indeed be a surprise to find an expression mechanism operating in the CAT system (or for any other family of resistance genes) which was not illustrative of a general strategy exploited by essential genes specifying biosynthetic or degradative functions. There may be some truth in referring to the cat structural gene as a "cartridge" for the isolation and manipulation of promoter functions. It would seem that nature has been at it for some time.
D000123:Acetyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D002701:Chloramphenicol / Q000494:pharmacology*; D015500:Chloramphenicol O-Acetyltransferase; D004352:Drug Resistance, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006706:Homeostasis
D002701:Chloramphenicol; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase