Mutations affecting the Rossman fold of isoleucyl-tRNA synthetase are correlated with low-level mupirocin resistance in Staphylococcus aureus.
The isoleucyl-tRNA synthetase (ileS) gene was sequenced in toto from 9 and in part from 31 Staphylococcus aureus strains with various degrees of susceptibility to mupirocin. All strains for which the mupirocin MIC was greater than 8 microg/ml contained point mutations affecting the Rossman fold via Val-to-Phe changes at either residue 588 (V588F) or residue 631 (V631F). The importance of the V588F mutation was confirmed by an allele-specific PCR survey of 32 additional strains. Additional mutations of uncertain significance were found in residues clustered on the surface of the IleS protein.
Antonio
Martin
M
Microbial Genomics and Pathogenesis Unit, Division of Immunity and Infection, The Medical School, University of Birmingham, Birmingham, BT15 2TT, United Kingdom.
McFerran
Neil
N
Pallen
Mark J
MJ
D019943:Amino Acid Substitution; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005998:Glycine / Q000235:genetics; D006801:Humans; D007533:Isoleucine-tRNA Ligase / Q000737:chemistry / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D016712:Mupirocin / Q000494:pharmacology; D009154:Mutation; D017354:Point Mutation; D017510:Protein Folding; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D013223:Statistics as Topic; D013912:Threonine / Q000235:genetics
D013912:Threonine; D016712:Mupirocin; D007533:Isoleucine-tRNA Ligase; D005998:Glycine