title: Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species.
abstract: Sulfonamide resistance in Neisseria meningitidis is mediated by altered forms of the chromosomal gene for the drug target enzyme dihydropteroate synthase. Sulfonamides have been used for decades both for prophylaxis and the treatment of meningococcal disease, and resistance is common. Two types of resistance determinants have been identified, and regions important for drug insusceptibility to the corresponding enzyme have been defined by site-directed mutagenesis. Both types of resistance traits have spread among strains of N. meningitidis of different serogroups and serotypes, and the large differences at the nucleotide level in a comparison of the resistance genes with the dhps genes of susceptible meningococci indicate the origin of one or maybe both types in other Neisseria species. One sulfonamide-sensitive strain of N. meningitidis was found to have a mosaic dhps gene with a central part identical to the corresponding part of a gonococcal strain. This observation supports the idea of an interspecies transfer of genetic material in Neisseria species as a mechanism for the development of chromosomally mediated resistance.
authors.affiliation: Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Fermer
authors.forename: B E
authors.initials: BE
authors.lastname: Kristiansen
authors.forename: O
authors.initials: O
authors.lastname: Sköld
authors.forename: G
authors.initials: G
authors.lastname: Swedberg
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005492:Folic Acid / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009344:Neisseria gonorrhoeae / Q000235:genetics; D009345:Neisseria meningitidis / Q000145:classification / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D012703:Serotyping; D013045:Species Specificity; D013329:Structure-Activity Relationship; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D013432:Sulfathiazoles; D013449:Sulfonamides; D005492:Folic Acid; D004094:Dihydropteroate Synthase; D000077589:Sulfathiazole