Population genomics ofBacillus anthracisfrom an anthrax hyperendemic area reveals transmission processes across spatial scales and unexpected within-host diversity
Authors: Forde Taya L. , Dennis Tristan P. W. , Aminu O. Rhoda , Harvey William T. , Hassim Ayesha , Kiwelu Ireen , Medvecky Matej , Mshanga Deogratius , Van Heerden Henriette , Vogel Adeline , Zadoks Ruth N. , Mmbaga Blandina T. , Lembo Tiziana , Biek Roman 
Published: September 2021

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 bacteriumBacillus anthracis, remains a threat to human and animal health and rural livelihoods in low- and middle-income countries. While the global genomic diversity ofB. anthracishas 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 single nucleotide polymorphisms (SNPs) among 73B. anthracisisolates derived from 33 livestock carcasses sampled over one year throughout the Ngorongoro Conservation Area, Tanzania, an area hyperendemic for anthrax. Genome-wide SNPs distinguished 22 uniqueB. anthracisgenotypes within the study area. However, phylogeographic 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 forB. anthracis, with an inoculum comprising multiple variants being the norm. Our work highlights that inferring transmission patterns ofB. anthracisfrom genomic data will require analytical approaches that account for extended and variable environmental persistence as well as co-infection.

Importance

Pathogens transmitted between animals and people affect the health and livelihoods of farmers, particularly in developing countries dependent on livestock. Understanding over what distances these pathogens are transmitted and how they evolve is important to inform control strategies towards reducing disease impacts. Information on the circulation ofBacillus anthracis, which causes the often-lethal disease anthrax, is lacking for settings where the disease is commonplace. Consequently, we examined its genetic variability in an area in Tanzania where anthrax is widespread. We found no clear link between how closely cases were sampled and their genetic similarity. We suspect this lack of congruence is primarily driven by large-scale livestock movements, which control efforts should take into consideration. Another significant finding was the co-occurrence of multipleB. anthracistypes within individual hosts, suggesting animals are commonly infected with a mixture of variants. This needs to be accounted for when investigating possible connections between cases.