Distribution of mutation frequencies among Salmonella enterica isolates from animal and human sources and genetic characterization of a Salmonella Heidelberg hypermutator

Abstract

Hypermutation is an important mechanism used by different Salmonella enterica subspecies enterica to regulate genetic stability in adaptation to changing environments, including antimicrobial treatments and industrial processes. Strong hypermutator strains generally contain a mutation in genes of the methyl mismatch repair (MMR) system and have mutation frequencies up to 1000-fold higher than wild type strains. The objectives of this study were to determine the distribution of mutation frequencies from a collection of 209 Salmonella strains, to genetically characterize a strong mutator, and to study MMR mutated protein–DNA binding interactions. Only one strain of S. Heidelberg was determined to have a hypermutator phenotype by virtue of its high mutation rate. Sequencing of genes of the MMR system showed a 12 bp deletion in the mutS gene was present. The MMR mutated protein-DNA binding interactions were studied by bioanalysis, using the available crystal structure of a similar MutS protein from Escherichia coli. This analysis showed the small deletion in the Salmonella MutS was localized within the core domain. A retardation assay with MutS from hypermutable and wild type strains showed this mutation has no effect on MutS DNA binding. A better understanding of the genetic mechanisms of hypermutation will help to anticipate the behavior of hypermutator strains in various conditions.