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.
Highlights
As genomic sequencing has become cheaper, faster, and more accessible, new application areas have opened
The power of genomic sequencing to analyze infectious disease outbreaks has been explored for several pathogens including Bacillus anthracis [2]
Our results demonstrate the power of genome analysis during a very confined outbreak situation as well as the limitations involved in resolving individual transmissions
Summary
As genomic sequencing has become cheaper, faster, and more accessible, new application areas have opened. In the emerging field of genomic epidemiology, ultra high-resolution Generation Sequencing (NGS) is used to distinguish different isolates from the same infectious disease outbreak [1]. The power of genomic sequencing to analyze infectious disease outbreaks has been explored for several pathogens including Bacillus anthracis [2]. In particular for Mycobacterium tuberculosis, it is even possible to resolve individual transmission events [3,4,5,6,7,8,9,10]. This type of high-resolution analysis of outbreak isolates gives insights into how mutation rates and microevolution reshape the genome during an infection. M. tuberculosis is an extremely slow growing bacterium with a long course of infection. We show how microevolution in a fast growing bacterium, B
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