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J Bacteriol. Aug 1995; 177(16): 4669–4675.
PMCID: PMC177231

Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species.


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.

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Selected References

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  • BERTANI G. Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli. J Bacteriol. 1951 Sep;62(3):293–300. [PMC free article] [PubMed]
  • Bjorvatn B, Lund V, Kristiansen BE, Korsnes L, Spanne O, Lindqvist B. Applications of restriction endonuclease fingerprinting of chromosomal DNA of Neisseria meningitidis. J Clin Microbiol. 1984 Jun;19(6):763–765. [PMC free article] [PubMed]
  • Bowler LD, Zhang QY, Riou JY, Spratt BG. Interspecies recombination between the penA genes of Neisseria meningitidis and commensal Neisseria species during the emergence of penicillin resistance in N. meningitidis: natural events and laboratory simulation. J Bacteriol. 1994 Jan;176(2):333–337. [PMC free article] [PubMed]
  • Brooks DR, Wang P, Read M, Watkins WM, Sims PF, Hyde JE. Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine. Eur J Biochem. 1994 Sep 1;224(2):397–405. [PubMed]
  • BROWN GM. The biosynthesis of folic acid. II. Inhibition by sulfonamides. J Biol Chem. 1962 Feb;237:536–540. [PubMed]
  • Dallas WS, Gowen JE, Ray PH, Cox MJ, Dev IK. Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100. J Bacteriol. 1992 Sep;174(18):5961–5970. [PMC free article] [PubMed]
  • Devereux J, Haeberli P, Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. [PMC free article] [PubMed]
  • Frosch M, Meyer TF. Transformation-mediated exchange of virulence determinants by co-cultivation of pathogenic Neisseriae. FEMS Microbiol Lett. 1992 Dec 15;100(1-3):345–349. [PubMed]
  • Jorgensen JH, Redding JS, Maher LA, Howell AW. Improved medium for antimicrobial susceptibility testing of Haemophilus influenzae. J Clin Microbiol. 1987 Nov;25(11):2105–2113. [PMC free article] [PubMed]
  • Kristiansen BE, Rådström P, Jenkins A, Ask E, Facinelli B, Sköld O. Cloning and characterization of a DNA fragment that confers sulfonamide resistance in a serogroup B, serotype 15 strain of Neisseria meningitidis. Antimicrob Agents Chemother. 1990 Nov;34(11):2277–2279. [PMC free article] [PubMed]
  • Lopez P, Espinosa M, Greenberg B, Lacks SA. Sulfonamide resistance in Streptococcus pneumoniae: DNA sequence of the gene encoding dihydropteroate synthase and characterization of the enzyme. J Bacteriol. 1987 Sep;169(9):4320–4326. [PMC free article] [PubMed]
  • Müller-Hill B, Crapo L, Gilbert W. Mutants that make more lac repressor. Proc Natl Acad Sci U S A. 1968 Apr;59(4):1259–1264. [PMC free article] [PubMed]
  • Rådström P, Fermér C, Kristiansen BE, Jenkins A, Sköld O, Swedberg G. Transformational exchanges in the dihydropteroate synthase gene of Neisseria meningitidis: a novel mechanism for acquisition of sulfonamide resistance. J Bacteriol. 1992 Oct;174(20):6386–6393. [PMC free article] [PubMed]
  • Rådström P, Swedberg G. RSF1010 and a conjugative plasmid contain sulII, one of two known genes for plasmid-borne sulfonamide resistance dihydropteroate synthase. Antimicrob Agents Chemother. 1988 Nov;32(11):1684–1692. [PMC free article] [PubMed]
  • Roland S, Ferone R, Harvey RJ, Styles VL, Morrison RW. The characteristics and significance of sulfonamides as substrates for Escherichia coli dihydropteroate synthase. J Biol Chem. 1979 Oct 25;254(20):10337–10345. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Sköld O. R-factor-mediated resistance to sulfonamides by a plasmid-borne, drug-resistant dihydropteroate synthase. Antimicrob Agents Chemother. 1976 Jan;9(1):49–54. [PMC free article] [PubMed]
  • Slock J, Stahly DP, Han CY, Six EW, Crawford IP. An apparent Bacillus subtilis folic acid biosynthetic operon containing pab, an amphibolic trpG gene, a third gene required for synthesis of para-aminobenzoic acid, and the dihydropteroate synthase gene. J Bacteriol. 1990 Dec;172(12):7211–7226. [PMC free article] [PubMed]
  • Sundström L, Rådström P, Swedberg G, Sköld O. Site-specific recombination promotes linkage between trimethoprim- and sulfonamide resistance genes. Sequence characterization of dhfrV and sulI and a recombination active locus of Tn21. Mol Gen Genet. 1988 Aug;213(2-3):191–201. [PubMed]
  • Swedberg G, Castensson S, Sköld O. Characterization of mutationally altered dihydropteroate synthase and its ability to form a sulfonamide-containing dihydrofolate analog. J Bacteriol. 1979 Jan;137(1):129–136. [PMC free article] [PubMed]
  • Swedberg G, Sköld O. Characterization of different plasmid-borne dihydropteroate synthases mediating bacterial resistance to sulfonamides. J Bacteriol. 1980 Apr;142(1):1–7. [PMC free article] [PubMed]
  • Swedberg G, Sköld O. Plasmid-borne sulfonamide resistance determinants studied by restriction enzyme analysis. J Bacteriol. 1983 Mar;153(3):1228–1237. [PMC free article] [PubMed]
  • Vandeyar MA, Weiner MP, Hutton CJ, Batt CA. A simple and rapid method for the selection of oligodeoxynucleotide-directed mutants. Gene. 1988 May 15;65(1):129–133. [PubMed]
  • Volpe F, Ballantine SP, Delves CJ. The multifunctional folic acid synthesis fas gene of Pneumocystis carinii encodes dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase. Eur J Biochem. 1993 Sep 1;216(2):449–458. [PubMed]
  • Yanisch-Perron C, Vieira J, Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. [PubMed]

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