Spontaneous mutators of salmonella typhimurium LT2 generated by insertion of transposable elements

Abstract

Spontaneous mutators of Salmonella typhimurium LT2 were generated by inserting the transposable element Tn5 or TnlO into the bacterial chromosome. Two mutators mapped at the position of the mutH and mutL loci of S. typhimurium, and two other mutators mapped at positions corresponding to the mutS and uvrD loci of Escherichia coli. A fifth mutator, mutB, did not map at a position corresponding to any of the known mutators of S. typhimurium or E. coli. The mutH,L,S and uvrD alleles increased the frequency of both spontaneous base substitution and frameshift mutations, whereas the mutB allele increased the frequency only of spontaneous base substitution mutations. The increased frequency of base substitution mutations was recA+ independent in the mutH, mutL, and uvrD strains and partially recA+ independent in the mutS strain. The uvrD mutation decreased the resistance of the cells to killing by ultraviolet irradiation. The mutH,L,S and uvrD strains showed an increased sensitivity to mutagenesis by the alkylating agents methyl methane sulfonate and ethyl methane sulfonate, but not to mutagenesis by 4-nitroquinoline-1-oxide.

Virulence and mutation rates of Salmonella typhimurium strains with increased mutagenic strength in a mouse model

“…1 shows how the S. typhimurium ATCC 14028 MutS 3 mutant presents about a 1000-fold increase in the frequency of spontaneous Nal R mutants over the wild-type strain. These values are in concordance with those obtained with transposoninduced MutS 3 mutants of S. typhimurium [16].…”

Heteroduplex deoxyribonucleic acid base mismatch repair in bacteria.

“…To check for the possible existence of independent mismatch repair pathways, mutation rates in multiple mutants were investigated (92). No additivity was observed for the four mut genes either in this study or when insertion mutants were isolated in these genes, in either E. coli (258) or Salmonella typhimurium (247).…”

“…As mentioned above, mutH, mutL, and mutS loci were initially identified on the basis of the mutator phenotype that they confer to the cells, and mutU was identified by its UV sensitivity (44). The spontaneous mutation rates of otherwise isogenic strains carrying mutations in mutH, mutL, mutS, and mutU were examined in a forward mutation assay in E. coli (92,225) and in Salmonella typhimurium (247). When compared with the wild type, these strains exhibited, for example, a 10 (mutU)to 165 (mutL)-fold increase in mutation rate to streptomycin resistance, and a 60 (mutU)to 1,300 (mutH)-fold increased mutation rate to valine resistance (92).…”

DNA base repair – recognition and initiation of catalysis

“…Investigations of the E. coli mutator strains mutS, mutL, mutH and uvrD revealed the molecular basis for MMR in prokaryotes (Nestmann, 1977;Shanabruch et al, 1981;Pang et al, 1985). The corresponding gene products comprise the MMRspecific MutS and MutL lesion recognition proteins, the MutH endonuclease and the DNA helicase II (UvrD).…”