[Mechanisms of endogenous drug resistance acquisition by spontaneous chromosomal gene mutation].
Endogenous resistance in bacteria is caused by a change or loss of function and generally genetically recessive. However, this type of resistance acquisition are now prevalent in clinical setting. Chromosomal genes that afford endogenous resistance are the genes correlated with the target of the drug, the drug inactivating enzymes, and permeability of the molecules including the antibacterial agents. Endogenous alteration of the drug target are mediated by the spontaneous mutation of their structural gene. This mutation provides much lower affinity of the drugs for the target. Gene expression of the inactivating enzymes, such as class C beta-lactamase, is generally regulated by regulatory genes. Spontaneous mutations in the regulatory genes cause constitutive enzyme production and provides the resistant to the agent which is usually stable for such enzymes. Spontaneous mutation in the structural gene gives the enzyme extra-spectrum substrate specificity, like ESBL (Extra-Spectrum-beta-Lactamase). Expression of structural genes encoding the permeability systems are also regulated by some regulatory genes. The spontaneous mutation of the regulatory genes reduce an amount of porin protein. This mutation causes much lower influx of the drug in the cell. Spontaneous mutation in promoter region of the structural gene of efflux protein was observed. This mutation raised the gene transcription and overproduced efflux protein. This protein progresses the drug efflux from the cell.
Fukuda
H
H
Department of Bacteriology, Juntendo University.
Hiramatsu
K
K
D001419:Bacteria / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D002463:Cell Membrane Permeability / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D009154:Mutation; D018272:Porins / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics
D001425:Bacterial Outer Membrane Proteins; D018272:Porins; D001618:beta-Lactamases