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.