Transformational exchanges in the dihydropteroate synthase gene of Neisseria meningitidis: a novel mechanism for acquisition of sulfonamide resistance.
The nucleotide sequences of the chromosomal dihydropteroate synthase (dhps) genes in sulfonamide-susceptible and sulfonamide-resistant strains of Neisseria meningitidis of serogroups A, B and C were determined. The molecular weights and the amino acid sequences showed similarity to those of all other known dihydropteroate synthase polypeptides. Sequence comparison of the N. meningitidis dhps genes indicated horizontal transfer of DNA segments rather than point mutations as the cause for resistance in meningococci. The dhps genes in three of four sulfonamide-resistant meningococci contained identical central regions of 424 bp. Compared with the corresponding genes in susceptible strains, each central region included an insert of 6 bp. In one of the sulfonamide-resistant strains, the dhps gene was similar to the corresponding genes in the sensitive strains in its NH2-terminal and C-terminal parts. Its central region, however, was identical to the corresponding regions of two of the other resistant genes, and thus it could be seen as a hybrid dhps gene. Transformation experiments and mapping of transformed dhps genes indicated the existence of a novel mechanism for the dissemination of sulfonamide resistance in N. meningitidis. The origin of the resistance-mediating segment of the gene is unknown, but hybridization results showed the presence of homologous dhps genes in Neisseria gonorrhoeae and N. lactamica but not in N. subflava or Branhamella catarrhalis.
Rådström
P
P
Chemical Center, Lund University, Sweden.
Fermér
C
C
Kristiansen
B E
BE
Jenkins
A
A
Sköld
O
O
Swedberg
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D013449:Sulfonamides / Q000494:pharmacology*; D014169:Transformation, Bacterial / Q000235:genetics*
D013449:Sulfonamides; D004094:Dihydropteroate Synthase