Fusidic acid resistance determinants in Staphylococcus aureus clinical isolates.
A total of 71 fusidic acid-resistant Staphylococcus aureus (45 methicillin-resistant and 26 methicillin-susceptible) isolates were examined for the presence of resistance determinants. Among 45 fusidic acid-resistant methicillin-resistant S. aureus (MRSA), isolates, 38 (84%) had fusA mutations conferring high-level resistance to fusidic acid (the MIC was ≥128 μg/ml for 22/38), none had fusB, and 7 (16%) had fusC. For 26 fusidic acid-resistant methicillin-susceptible S. aureus (MSSA), only 3 possessed fusA mutations, but 15 (58%) had fusB and 8 (31%) had fusC. Low-level resistance to fusidic acid (MICs ≤ 32 μg/ml) was found in most fusB- or fusC-positive isolates. For 41 isolates (38 MRSA and 3 MSSA), with fusA mutations, a total of 21 amino acid substitutions in EF-G (fusA gene) were detected, of which R76C, E444K, E444V, C473S, P478S, and M651I were identified for the first time. The nucleotide sequencing of fusB and flanking regions in an MSSA isolate revealed the structure of partial IS257-aj1-LP-fusB-aj2-aj3-IS257-partial blaZ, which is identical to the corresponding region in pUB101, and the rest of fusB-carrying MSSA isolates also show similar structures. On the basis of spa and staphylococcal cassette chromosome mec element (SCCmec) typing, two major genotypes, spa type t037-SCCmec type III (t037-III; 28/45; 62%) and t002-II (13/45; 29%), were predominant among 45 MRSA isolates. By pulsed-field gel electrophoresis analysis, 45 MRSA isolates were divided into 12 clusters, while 26 MSSA isolates were divided into 15 clusters. Taken together, the distribution of fusidic acid resistance determinants (fusA mutations, fusB, and fusC) was quite different between MRSA and MSSA groups.
Chen
Hsiao-Jan
HJ
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 100, Taiwan.
Hung
Wei-Chun
WC
Tseng
Sung-Pin
SP
Tsai
Jui-Chang
JC
Hsueh
Po-Ren
PR
Teng
Lee-Jene
LJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015139:Blotting, Southern; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D005672:Fusidic Acid / Q000494:pharmacology*; D016106:Methicillin Resistance / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009154:Mutation; D020653:Peptide Elongation Factor G / Q000235:genetics; D016133:Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C492444:FusA protein, Staphylococcus aureus; D020653:Peptide Elongation Factor G; D005672:Fusidic Acid