title: Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae.
abstract: The genetic basis of sulfonamide resistance in six clinical isolates of Streptococcus pneumoniae was demonstrated to be 3- or 6-bp duplications within sulA, the chromosomal gene encoding dihydropteroate synthase. The duplications all result in repetition of one or two amino acids in the region from Arg58 to Tyr63, close to but distinct from the sul-d mutation, a duplication previously reported in a resistant laboratory strain (P. Lopez, M. Espinosa, B. Greenberg, and S. A. Lacks, J. Bacteriol. 169:4320-4326, 1987). Six sulfonamide-susceptible clinical isolates lacked such duplications. The role of the duplications in conferring sulfonamide resistance was confirmed by transforming 319- or 322-bp PCR fragments into the chromosome of a susceptible recipient. Two members of a clone of serotype 9V, one susceptible and one resistant to sulfonamide, which are highly related by other criteria, were shown to have sulA sequences that differ in 7.2% of nucleotides in addition to the duplication responsible for resistance. It is postulated that horizontal gene exchange has been involved in the acquisition (or loss) of resistance within this clone. However, five of the six resistant isolates have distinct duplications and other sequence polymorphisms, suggesting that resistance has arisen independently on many occasions.
authors.affiliation: Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, United Kingdom. J.Maskell@mds.qmw.ac.uk
authors.forename: J P
authors.initials: JP
authors.lastname: Maskell
authors.forename: A M
authors.initials: AM
authors.lastname: Sefton
authors.forename: L M
authors.initials: LM
authors.lastname: Hall
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D017931:DNA Primers; D004269:DNA, Bacterial / Q000302:isolation & purification; D004094:Dihydropteroate Synthase / Q000096:biosynthesis / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D011008:Pneumococcal Infections / Q000235:genetics / Q000382:microbiology; D016133:Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D017931:DNA Primers; D004269:DNA, Bacterial; D013449:Sulfonamides; D004094:Dihydropteroate Synthase