Novel dihydrofolate reductases isolated from epidemic strains of trimethoprim/sulfamethoxazole-resistant Shigella sonnei.
Two strains of trimethoprim-resistant Shigella sonnei bearing R plasmids pBH600 and pBH700 each elaborated a dihydrofolate reductase (DHFR) and were moderately resistant to trimethoprim (minimum inhibitory concentrations, 128 and 256 micrograms/ml, respectively). Neither plasmid hybridized to probes for DHFR types I, II, or III. The trimethoprim resistance genes from the R plasmids resided on a 1600-base pair (bp) PstI fragment of pBH600 and an 1800-bp PstI fragment of pBH700. Isoelectric focusing showed distinct isoelectric points for the enzymes coded for on pBH600 (5.3) and pBH700 (5.6-5.7). Trimethoprim-resistant S. sonnei from 10 locations in nine states were examined. Isolates from 8 locations hybridized only to a pBH700-derived probe and one isolate hybridized to a pBH600-derived probe. These two trimethoprim resistance genes appear novel. The gene on plasmid pBH700 codes for an enzyme that seems widespread among S. sonnei isolates in the USA.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
N L
NL
Barg
F S
FS
Hutson
L A
LA
Wheeler
C J
CJ
Thomson
S G
SG
Amyes
M
M
Wharton
W
W
Schaffner
D000668:Ampicillin Resistance; D015139:Blotting, Southern; D002702:Chloramphenicol Resistance; D015342:DNA Probes; D004269:DNA, Bacterial / Q000032:analysis; D004196:Disease Outbreaks; D004405:Dysentery, Bacillary / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009657:North Carolina / Q000453:epidemiology; D009693:Nucleic Acid Hybridization; D011815:R Factors; D012764:Shigella sonnei / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D013714:Tennessee / Q000453:epidemiology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000302:isolation & purification*; D014296:Trimethoprim Resistance / Q000235:genetics; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
D015342:DNA Probes; D004269:DNA, Bacterial; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D013762:Tetrahydrofolate Dehydrogenase