title: Microevolution during an Anthrax outbreak leading to clonal heterogeneity and penicillin resistance.
abstract: Anthrax is a bacterial disease primarily affecting grazing animals but it can also cause severe disease in humans. We have used genomic epidemiology to study microevolution of the bacterium in a confined outbreak in cattle which involved emergence of an antibiotic-resistant phenotype. At the time of death, the animals contained a heterogeneous population of Single Nucleotide Variants (SNVs), some being clonal but most being subclonal. We found that independent isolates from the same carcass had similar levels of SNV differences as isolates from different animals. Furthermore the relative levels of subclonal populations were different in different locations in the same carcass. The heterogeneity appeared to be derived in part from heterogeneity in the infectious dose. The resistance phenotype was linked to clonal mutations in an anti-sigma factor gene and in one case was preceded by an acquisition of a hypermutator phenotype. In another animal, small subclonal populations were observed with counteracting mutations that had turned off the resistance genes. In summary, this study shows the importance of accounting for both acquired and inherited heterogeneity when doing high-resolution infection tracing and when estimating the risks associated with penicillin treatment.
authors.affiliation: Department of Bacteriology, National Veterinary Institute (SVA), Uppsala, Sweden ; Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Ågren
authors.affiliation: Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Finn
authors.affiliation: Department of Animal Health and Antimicrobial Strategies, National Veterinary Institute (SVA), Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Bengtsson
authors.affiliation: Department of Bacteriology, National Veterinary Institute (SVA), Uppsala, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Segerman
mesh_terms: D000818:Animals; D000881:Anthrax / Q000453:epidemiology / Q000382:microbiology / Q000662:veterinary*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001408:Bacillus anthracis / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases; D002999:Clone Cells; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D019143:Evolution, Molecular; D018740:Genetic Heterogeneity; D005838:Genotype; D006790:Host-Parasite Interactions; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013548:Sweden / Q000453:epidemiology
chemical_list: D000900:Anti-Bacterial Agents