Identical genes for trimethoprim‐resistant dihydrofolate reductase from Staphylococcus aureus in Australia and Central Europe

Abstract

The nucleotide sequence of a 1.25 kb BglII/EcoRI fragment from the 34 kb trimethoprim (Tp)-resistant plasmid pABU1 of Staphylococcus aureus 157/4696, isolated in Zürich, was determined. It contained the entire Tp-resistant dihydrofolate reductase gene, 197 bp of the thymidylate synthetase, 395 bp of a truncated gene and 111 bp of IS257R1. With the exception of one single base pair at position of 862 the sequence of the whole fragment was identical to nucleotides 1633 to 2885 of the Tp-resistant transposon Tn4003 in plasmid pSK1 from an Australian S. aureus isolate. This suggests the worldwide dissemination of Tn4003 in multiresistant Staphylococci.

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?

“…Recently, we described a plasmid-encoded Tmp r DHFR from a clinical isolate of S. aureus (10), and even though the plasmid differed from those described elsewhere (25,32), the dfr gene was found to be identical in sequence to the dfrA gene from an Australian isolate (32). This surprisingly high level of sequence conservation was explained by the worldwide spread of transposon Tn4003, in which the gene is located (32).…”

“…Recently, a plasmid-encoded TMP-resistant (Tmp r ) DHFR (S1 DHFR) from a clinical isolate of S. aureus has been described (10). Despite the fact that this strain was isolated in Zürich, Switzerland, and that the plasmid differed from those found elsewhere (25,32), the sequence of the DHFR gene was found to be identical to that of a DHFR gene from an Australian isolate (32).…”

Characterization of the gene for chromosomal trimethoprim-sensitive dihydrofolate reductase of Staphylococcus aureus ATCC 25923

“…(19), carrying the precursor operon thyE-dfrA-ORF140. Since the N-terminal amino acid sequence of the Tmps chromosomal S. aureus DHFR had been deduced (11) and in view of the high degree of homology at the N terminus between the Tmpr and Tmps DHFR molecules, it was also speculated that the Tmpr DHFR may have evolved from the chromosomal gene by mutation and mobilization (5 (Fig. 1) matches the sequence determined for purified S. aureus DHFR (11).…”

“…An S. aureus plasmid-encoded Tmp-resistant (Tmpr) DHFR with an approximate molecular mass of 18 kDa has recently been characterized by Burdeska et al (5). Previous studies have shown that this gene, which was also found on transposon Tn4003 (19), is present in isolates in Europe and Australia (5).…”

“…Previous studies have shown that this gene, which was also found on transposon Tn4003 (19), is present in isolates in Europe and Australia (5). The origin of this gene, termed dfrA, is unknown, and the gene for the chromosomal DHFR of S. aureus has not yet been identified.…”