CHARACTERIZATION OF THE GENE FOR THE CHROMOSOMAL DIHYDROFOLATE-REDUCTASE (DHFR) OF STAPHYLOCOCCUS-EPIDERMIDIS ATCC-14990 - THE ORIGIN OF THE TRIMETHOPRIM-RESISTANT S1 DHFR FROM STAPHYLOCOCCUS-AUREUS

被引:59
作者
DALE, GE
BROGER, C
HARTMAN, PG
LANGEN, H
PAGE, MGP
THEN, RL
STUBER, D
机构
[1] F HOFFMANN LA ROCHE & CO LTD, PHARMACEUT RES, DEPT GENE TECHNOL, CH-4002 BASEL, SWITZERLAND
[2] F HOFFMANN LA ROCHE & CO LTD, PHARMACEUT RES, DEPT COMPUTAT & STRUCT CHEM, CH-4002 BASEL, SWITZERLAND
[3] F HOFFMANN LA ROCHE & CO LTD, PHARMACEUT RES, DEPT INFECT DIS, CH-4002 BASEL, SWITZERLAND
关键词
D O I
10.1128/jb.177.11.2965-2970.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The gene for the chromosomally encoded dihydrofolate reductase (DHFR) of Staphylococcus epidermidis ATCC 14990 has been cloned and characterized. The structural gene encodes a polypeptide of 161 amino acid residues with a calculated molecular weight of 18,417. This trimethoprim-sensitive (Tmp(s)) DHFR, SeDHFR, differs in only three amino acids (Val-31-->Ile, Gly-43-->Ala, and Phe-98-->Tyr) from the trimethoprim-resistant (Tmp(r)) S1 DHFR encoded by transposon Tn4003. Since in addition the S. epidermidis gene also forms part of an operon with thyE and open reading frame 140 as in Tn4003, the chromosomally located gene encoding the Tmp(s) SeDHFR is likely to be the molecular origin of the plasmid-located gene encoding the Tmp(r) S1 DHFR Site-directed mutagenesis and kinetic analysis of the purified enzymes suggest that a single Phe-->Tyr change at position 98 is the major determinant of trimethoprim resistance.
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页码:2965 / 2970
页数:6
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