Microevolution during an Anthrax outbreak leading to clonal heterogeneity and penicillin resistance.

Ă…gren J, Finn M, Bengtsson B, Segerman B

PLoS ONE 9 (2) e89112 [2014-02-13; online 2014-02-13]

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.

NGI Stockholm (Genomics Applications)

NGI Stockholm (Genomics Production)

NGI Uppsala (SNP&SEQ Technology Platform)

QC bibliography QC xrefs

PubMed 24551231

DOI 10.1371/journal.pone.0089112

Crossref 10.1371/journal.pone.0089112

GENBANK CP006742

GENBANK CP006743

GENBANK CP006744

RefSeq NC_007530

PONE-D-13-49633

pmc PMC3923885