Biomaterial Database

Monitoring of plasmid-encoded, trimethoprim-resistant dihydrofolate reductase genes: detection of a new resistant enzyme. 1982

M E Fling, and L Walton, and L P Elwell

Using-gene-specific radiolabeled probe DNAs, we analyzed 42 clinical bacterial isolates with high-level trimethoprim (Tp) resistance for the presence of a type I or a type II plasmid-specified dihydrofolate reductase (DHFR) gene. Plasmid DNA from 17 strains harbored a type I DHFR, whereas 11 isolates contained plasmids that harbored a type II DHFR structural gene. The plasmid DNAs from five strains appeared to hybridize with both type I and type II DHFR probe DNAs. In addition, eight isolates had type I resistance determinants integrated into the chromosomes, presumably on transposon 7 (Tn7). Among the strains analyzed in this survey, none of the chromosomally located, Tp-insensitive reductases were of the type II class. Both the plasmid and chromosomal DNAs of one isolate showed no homology with either the type I or type II DHFR probe DNA. The plasmid harbored by this strain encoded a "new" Tp-resistant enzyme that differed significantly, both in molecular weight and with respect to trimethoprim and methotrexate inhibition kinetics, from the previously characterized plasmid-associated dihydrofolate reductases.

UI	MeSH Term	Description	Entries
D011815	R Factors	A class of plasmids that transfer antibiotic resistance from one bacterium to another by conjugation.	R Factor,R Plasmid,R Plasmids,Resistance Factor,Resistance Factors,Factor, R,Factor, Resistance,Factors, R,Factors, Resistance,Plasmid, R,Plasmids, R
D004269	DNA, Bacterial	Deoxyribonucleic acid that makes up the genetic material of bacteria.	Bacterial DNA
D005796	Genes	A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.	Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D001419	Bacteria	One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.	Eubacteria
D013762	Tetrahydrofolate Dehydrogenase	An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.	Dihydrofolate Dehydrogenase,Dihydrofolate Reductase,Folic Acid Reductase,Acid Reductase, Folic,Dehydrogenase, Dihydrofolate,Dehydrogenase, Tetrahydrofolate,Reductase, Dihydrofolate,Reductase, Folic Acid
D014295	Trimethoprim	A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.	Proloprim,Trimpex