Population genomics of Bacillus anthracis from an anthrax hyperendemic area reveals transmission processes across spatial scales and unexpected within-host diversity

Abstract

Genomic sequencing has revolutionized our understanding of bacterial disease epidemiology, but remains underutilized for zoonotic pathogens in remote endemic settings. Anthrax, caused by the spore-forming bacterium Bacillus anthracis , remains a threat to human and animal health and rural livelihoods in low- and middle-income countries. While the global genomic diversity of B. anthracis has been well-characterized, there is limited information on how its populations are genetically structured at the scale at which transmission occurs, critical for understanding the pathogen’s evolution and transmission dynamics. Using a uniquely rich dataset, we quantified genome-wide SNPs among 73 B. anthracis isolates derived from 33 livestock carcasses sampled over 1 year throughout the Ngorongoro Conservation Area, Tanzania, a region hyperendemic for anthrax. Genome-wide SNPs distinguished 22 unique B. anthracis genotypes (i.e. SNP profiles) within the study area. However, phylogeographical structure was lacking, as identical SNP profiles were found throughout the study area, likely the result of the long and variable periods of spore dormancy and long-distance livestock movements. Significantly, divergent genotypes were obtained from spatio-temporally linked cases and even individual carcasses. The high number of SNPs distinguishing isolates from the same host is unlikely to have arisen during infection, as supported by our simulation models. This points to an unexpectedly wide transmission bottleneck for B. anthracis , with an inoculum comprising multiple variants being the norm. Our work highlights that inferring transmission patterns of B. anthracis from genomic data will require analytical approaches that account for extended and variable environmental persistence, as well as co-infection.

Pathogen genomics and One Health: a scoping review of current practices in zoonotic disease research

“…Genomic advances have transformed both fundamental research and public health surveillance of bacterial pathogens, particularly foodborne agents (e.g., E. coli and S. enterica ) which have become pilot organisms for routine whole-genome sequencing and genomic epidemiology studies (Gilchrist et al , 2015; Allard et al , 2016). Genomic studies paired with phylogenetic approaches can reconstruct recent epidemic histories, providing insight into potential sources and timing of pathogen emergence, transmission events and pathways that may be contextualised temporally and spatially (Faria et al , 2017; Ridenour et al , 2021; Forde et al , 2022). To date, genomic epidemiology, and phylodynamics in particular, seemed to be more restricted to single-stranded RNA viruses owing to their small, rapidly mutating genomes, which require lower sequencing effort to detect contemporary phylogenetic signal (Fountain-Jones et al , 2018; Ingle et al , 2021).…”

“…We deliberately chose to limit our screening to studies that included genomic sequencing of specimens from human hosts. Therefore, we omitted the substantial body of work integrating genomics to decipher pathogen transmission among multiple non-human vertebrate hosts and at the animal-environment interface (e.g., Bennett et al , 2020; Forde et al , 2022).…”

Plasmid-mediated colistin resistance among human clinical Enterobacterales isolates: national surveillance in the Czech Republic

“…Remaining detailed tree topology was constructed based on a pipeline described in a previous study ( Forde et al, 2022 ) using Python scripts that are available on GitHub. 6 Based on the E. coli ST744 global tree, 38 Illumina SRA archives belonging to isolates that were closely related to 10 ST744 isolates from our collection were gathered from the GenBank database in May 2021.…”

Plasmid-mediated colistin resistance among human clinicalEnterobacteralesisolates: National surveillance in the Czech Republic

“…1.11 (Price et al, 2010) compiled with double precision arithmetic. Remaining detailed tree topology was constructed based on a pipeline described in previous study (Forde et al, 2022) using Python scripts that are available on GitHub (https://github.com/matejmedvecky/anthraxdiversityscripts). Based on E. coli ST744 global tree, 38 Illumina SRA archives belonging to isolates that were closely related to ten ST744 isolates from our collection were gathered from the GenBank database in May 2021.…”