Trimethoprim Resistance and Susceptibility Genes in Staphylococcus epidermidis

Abstract

Genes encoding trimethoprim (TMP)-resistant and -susceptible dihydrofolate reductases (DHFR) in Staphylococcus epidermidis isolated in Saitama Prefecture were compared with the TMP-resistant DHFR gene of S. aureus, dfrA. The nucleotide sequences of TMP r and TMPs genes in five S. epidermidis isolates tested could be divided into three types: type 1, identical with the TMPr gene dfrA that had been found in S. aureus; type 3, identical with the TMP s gene dfrC in S. epidermidis; and type 2, having only two nucleotide substitutions to dfrC with no amino acid change. TMP r isolates carried either one of the type 2 or type 3 sequences in addition to the type 1 sequence. A Southern hybridization analysis revealed that, in TMP r S. epidermidis, the type 1 sequence was located on a 5.5 kb EcoRI-EcoRV restriction fragment together with the sequence for the gentamicin (GM)-resistant gene, while the type 2 or type 3 sequence was located on the 1.0 kb EcoRI-EcoRV fragment. No plasmid-carrying dfrA-homologous sequence was detected in the S. epidermidis isolates we tested. These results suggest that the TMP r and GM r genes are closely linked and located on the chromosome in S. epidermidis isolated in Japan.

Whole genome sequencing revealed new molecular characteristics in multidrug resistant staphylococci recovered from high frequency touched surfaces in London

“…epidermidis isolates were quite similar in their antibiotic resistance profile from our hierarchy clustering analysis even if they came from different areas. This may be due to that all isolates had the fluoroquinolone efflux pump gene norA and trimethoprim resistance dihydrofolate reductase gene dfrC 40,41 . It is possible that these genes are essential for S .…”

Antibiotic multiresistance strictly associated with IS256 and ica genes in Staphylococcus epidermidis strains from implant orthopedic infections

“…Noticeably, Tn 4001 was identified in the ica ‐positive biofilm‐producing S. epidermidis RP62A, but not in S. epidermidis ATCC 12228, which is rather a commensal, ica ‐negative, non‐biofilm producing strain 22. Totake et al23 have described a composite transposon that confers resistance to trimethoprim and gentamicin in S. epidermidis . Such a composite transposon of 8.5 kb (full sequence is reported in GenBank; Accession: AB049452) consists of a Tn 4003 transposon, typically including the dfrA gene for the trimethoprim resistance dihydrofolate reductase, in which an entire Tn 4001 transposon flanked by IS 256 sequences has been inserted.…”

“…Such a composite transposon of 8.5 kb (full sequence is reported in GenBank; Accession: AB049452) consists of a Tn 4003 transposon, typically including the dfrA gene for the trimethoprim resistance dihydrofolate reductase, in which an entire Tn 4001 transposon flanked by IS 256 sequences has been inserted. Since most of CoNS isolates are generally resistant to sulfamethoxazole, the resistance to the sulfamethoxazole–trimethoprim combination is closely related to the presence of trimethoprim resistance determinants 23. The presence of either the Tn 4001 transposon or the above described composite transposon in the genome of clinical S. epidermidis strains may therefore contribute to explain the association between IS 256 and phenotypic resistance to aminoglycosides and sulfamethoxazole (+trimethoprim).…”

The anticancer chemotherapy drug 5-Fluorouracil has positive interaction with antibiotics and can select for antibiotic resistance inStaphylococcus aureus

“…We also tested our strains for susceptibility to trimethoprim, sulphamethoxazole and co-trimoxazole. The strain F77 was found to be clinically resistant to trimethoprim, sulphamethoxazole, cotrimoxazole (potentially due to the carriage of dfrC (34)), and also had decreased susceptibility to 5-FU (Table 1). In contrast, strain NCTC 6571 was susceptible to all of these antibiotics with increased sensitivity to 5-FU (Table 1).…”