Yersinia pestis is transmitted from fleas to rodents when the bacterium develops an extensive biofilm in the foregut of a flea, starving it into a feeding frenzy, or, alternatively, during a brief ...period directly after feeding on a bacteremic host. These two transmission modes are in a trade-off regulated by the amount of biofilm produced by the bacterium. Here by investigating 446 global isolated Y. pestis genomes, including 78 newly sequenced isolates sampled over 40 years from a plague focus in China, we provide evidence for strong selection pressures on the RNA polymerase ω-subunit encoding gene rpoZ. We demonstrate that rpoZ variants have an increased rate of biofilm production in vitro, and that they evolve in the ecosystem during colder and drier periods. Our results support the notion that the bacterium is constantly adapting-through extended phenotype changes in the fleas-in response to climate-driven changes in the niche.
Significance The second plague pandemic in medieval Europe started with the Black Death epidemic of 1347–1353 and killed millions of people over a time span of four centuries. It is commonly thought ...that after its initial introduction from Asia, the disease persisted in Europe in rodent reservoirs until it eventually disappeared. Here, we show that climate-driven outbreaks of Yersinia pestis in Asian rodent plague reservoirs are significantly associated with new waves of plague arriving into Europe through its maritime trade network with Asia. This association strongly suggests that the bacterium was continuously reimported into Europe during the second plague pandemic, and offers an alternative explanation to putative European rodent reservoirs for how the disease could have persisted in Europe for so long.
The Black Death, originating in Asia, arrived in the Mediterranean harbors of Europe in 1347 CE, via the land and sea trade routes of the ancient Silk Road system. This epidemic marked the start of the second plague pandemic, which lasted in Europe until the early 19th century. This pandemic is generally understood as the consequence of a singular introduction of Yersinia pestis , after which the disease established itself in European rodents over four centuries. To locate these putative plague reservoirs, we studied the climate fluctuations that preceded regional plague epidemics, based on a dataset of 7,711 georeferenced historical plague outbreaks and 15 annually resolved tree-ring records from Europe and Asia. We provide evidence for repeated climate-driven reintroductions of the bacterium into European harbors from reservoirs in Asia, with a delay of 15 ± 1 y. Our analysis finds no support for the existence of permanent plague reservoirs in medieval Europe.
ABSTRACT
Environmentally transmitted diseases are comparatively poorly understood and managed, and their ecology is particularly understudied. Here we identify challenges of studying environmental ...transmission and persistence with a six‐sided interdisciplinary review of the biology of anthrax (Bacillus anthracis). Anthrax is a zoonotic disease capable of maintaining infectious spore banks in soil for decades (or even potentially centuries), and the mechanisms of its environmental persistence have been the topic of significant research and controversy. Where anthrax is endemic, it plays an important ecological role, shaping the dynamics of entire herbivore communities. The complex eco‐epidemiology of anthrax, and the mysterious biology of Bacillus anthracis during its environmental stage, have necessitated an interdisciplinary approach to pathogen research. Here, we illustrate different disciplinary perspectives through key advances made by researchers working in Etosha National Park, a long‐term ecological research site in Namibia that has exemplified the complexities of the enzootic process of anthrax over decades of surveillance. In Etosha, the role of scavengers and alternative routes (waterborne transmission and flies) has proved unimportant relative to the long‐term persistence of anthrax spores in soil and their infection of herbivore hosts. Carcass deposition facilitates green‐ups of vegetation to attract herbivores, potentially facilitated by the role of anthrax spores in the rhizosphere. The underlying seasonal pattern of vegetation, and herbivores' immune and behavioural responses to anthrax risk, interact to produce regular ‘anthrax seasons’ that appear to be a stable feature of the Etosha ecosystem. Through the lens of microbiologists, geneticists, immunologists, ecologists, epidemiologists, and clinicians, we discuss how anthrax dynamics are shaped at the smallest scale by population genetics and interactions within the bacterial communities up to the broadest scales of ecosystem structure. We illustrate the benefits and challenges of this interdisciplinary approach to disease ecology, and suggest ways anthrax might offer insights into the biology of other important pathogens. Bacillus anthracis, and the more recently emerged Bacillus cereus biovar anthracis, share key features with other environmentally transmitted pathogens, including several zoonoses and panzootics of special interest for global health and conservation efforts. Understanding the dynamics of anthrax, and developing interdisciplinary research programs that explore environmental persistence, is a critical step forward for understanding these emerging threats.
Bacillus anthracis, the etiological agent of anthrax, is a well-established model organism. For B. anthracis and most other infectious diseases, knowledge regarding transmission and infection ...parameters in natural systems, in large part, comprises data gathered from closely controlled laboratory experiments. Fatal, natural anthrax infections transmit the bacterium through new host−pathogen contacts at carcass sites, which can occur years after death of the previous host. For the period between contact and death, all of our knowledge is based upon experimental data from domestic livestock and laboratory animals. Here we use a noninvasive method to explore the dynamics of anthrax infections, by evaluating the terminal diversity of B. anthracis in anthrax carcasses. We present an application of population genetics theory, specifically, coalescence modeling, to intrainfection populations of B. anthracis to derive estimates for the duration of the acute phase of the infection and effective population size converted to the number of colony-forming units establishing infection in wild plains zebra (Equus quagga). Founding populations are small, a few colony-forming units, and infections are rapid, lasting roughly between 1 d and 3 d in the wild. Our results closely reflect experimental data, showing that small founding populations progress acutely, killing the host within days. We believe this method is amendable to other bacterial diseases from wild, domestic, and human systems.
Anthrax, caused by the bacterium Bacillus anthracis, is a disease of historical and current importance that is found throughout the world. The basis of its historical transmission is anecdotal and ...its true global population structure has remained largely cryptic. Seven diverse B. anthracis strains were whole-genome sequenced to identify rare single nucleotide polymorphisms (SNPs), followed by phylogenetic reconstruction of these characters onto an evolutionary model. This analysis identified SNPs that define the major clonal lineages within the species. These SNPs, in concert with 15 variable number tandem repeat (VNTR) markers, were used to subtype a collection of 1,033 B. anthracis isolates from 42 countries to create an extensive genotype data set. These analyses subdivided the isolates into three previously recognized major lineages (A, B, and C), with further subdivision into 12 clonal sub-lineages or sub-groups and, finally, 221 unique MLVA15 genotypes. This rare genomic variation was used to document the evolutionary progression of B. anthracis and to establish global patterns of diversity. Isolates in the A lineage are widely dispersed globally, whereas the B and C lineages occur on more restricted spatial scales. Molecular clock models based upon genome-wide synonymous substitutions indicate there was a massive radiation of the A lineage that occurred in the mid-Holocene (3,064-6,127 ybp). On more recent temporal scales, the global population structure of B. anthracis reflects colonial-era importation of specific genotypes from the Old World into the New World, as well as the repeated industrial importation of diverse genotypes into developed countries via spore-contaminated animal products. These findings indicate humans have played an important role in the evolution of anthrax by increasing the proliferation and dispersal of this now global disease. Finally, the value of global genotypic analysis for investigating bioterrorist-mediated outbreaks of anthrax is demonstrated.
Heterogeneous aggregation of parasites between individual hosts is common and regarded as an important factor in understanding transmission dynamics of vector-borne diseases. Lyme disease is vectored ...by generalist tick species, yet we have a limited understanding of how individual heterogeneities within small mammal host populations affect the aggregation of ticks and likelihood of infection. Male hosts often have higher parasite and infection levels than females, but whether this is linked to sexual body size dimorphism remains uncertain. Here, we analysed how host species, sex, and body mass influenced
Ixodes ricinus
tick infestations and the infection prevalence of
Borrelia burgdorferi
sensu lato (s.l.) in three species of small mammals involved in the enzootic transmission cycle of Lyme disease in Norway from 2018 to 2022. Larval and nymphal ticks were found on 98% and 34% of all individual hosts, respectively. In bank voles and wood mice, both larval and nymphal tick infestation and infection probability increased with body mass, and it increased more with mass for males than for females. Tick infestation in the common shrew increased with body mass and was higher in males, while pathogen infection was higher in females. Sex-biases in infestation did not correspond with level of sexual body mass dimorphism across species. This study contributes to our understanding of how individual heterogeneity among small mammalian hosts influences
I. ricinus
tick aggregation and prevalence of
B. burgdorferi
s.l. at northern latitudes.
The association of historical plague pandemics with Yersinia pestis remains controversial, partly because the evolutionary history of this largely monomorphic bacterium was unknown. The ...microevolution of Y. pestis was therefore investigated by three different multilocus molecular methods, targeting genomewide synonymous SNPs, variation in number of tandem repeats, and insertion of IS100 insertion elements. Eight populations were recognized by the three methods, and we propose an evolutionary tree for these populations, rooted on Yersinia pseudotuberculosis. The tree invokes microevolution over millennia, during which enzootic pestoides isolates evolved. This initial phase was followed by a binary split 6,500 years ago, which led to populations that are more frequently associated with human disease. These populations do not correspond directly to classical biovars that are based on phenotypic properties. Thus, we recommend that henceforth groupings should be based on molecular signatures. The age of Y. pestis inferred here is compatible with the dates of historical pandemic plague. However, it is premature to infer an association between any modern molecular grouping and a particular pandemic wave that occurred before the 20th century.
Emergence of tick-borne diseases is impacting humans and livestock across the Northern Hemisphere. There are, however, large regional variations in number of cases of tick-borne diseases. Some areas ...have surprisingly few cases of disease compared to other regions. The aim here is to provide a first step towards a better understanding of such contrasting regional patterns of disease emergences at the northern distribution range of Ixodes ricinus in Europe.
We compare disease incidence, vector abundance and pathogen prevalence in eastern and western Norway differing in the number of tick-borne disease cases. First, we analysed the incidence of Lyme borreliosis in humans, tick-borne fever (anaplasmosis) in sheep and anaplasmosis and babesiosis in cattle to verify if incidence differed. Secondly, we analysed extensive field data on questing tick density, pathogen prevalence, as well as the broad spatial pattern of human and livestock distribution as it may relate to tick exposure.
The incidences of all diseases were lower in eastern, compared to western, Norway, but this was most marked for the livestock diseases. While the prevalence of Borrelia burgdorferi (sensu lato) in ticks was similar in the two regions, the prevalence of Anaplasma phagocytophilum was markedly lower in eastern, compared to western, Norway. We found overall a lower abundance of questing nymphs in the east. In the east, there were cases of babesiosis in cattle where anaplasmosis was absent, suggesting absence of the pathogen rather than differences in exposure to ticks as part of the explanation for the much lower incidence of anaplasmosis in eastern Norway.
Many factors contribute to different disease incidence across ecosystems. We found that regional variation in tick-borne disease incidence may be partly linked to vector abundance and pathogen prevalence, but differently for human and livestock diseases. Further studies are needed to determine if there is also regional variation in specific genospecies and strain frequencies differing in pathogenicity.
Anthrax is a globally distributed disease affecting primarily herbivorous mammals. It is caused by the soil-dwelling and spore-forming bacterium Bacillus anthracis. The dormant B. anthracis spores ...become vegetative after ingestion by grazing mammals. After killing the host, B. anthracis cells return to the soil where they sporulate, completing the lifecycle of the bacterium. Here we present the first study describing temporal microbial soil community changes in Etosha National Park, Namibia, after decomposition of two plains zebra (Equus quagga) anthrax carcasses. To circumvent state-associated-challenges (i.e. vegetative cells/spores) we monitored B. anthracis throughout the period using cultivation, qPCR and shotgun metagenomic sequencing.
The combined results suggest that abundance estimation of spore-forming bacteria in their natural habitat by DNA-based approaches alone is insufficient due to poor recovery of DNA from spores. However, our combined approached allowed us to follow B. anthracis population dynamics (vegetative cells and spores) in the soil, along with closely related organisms from the B. cereus group, despite their high sequence similarity. Vegetative B. anthracis abundance peaked early in the time-series and then dropped when cells either sporulated or died. The time-series revealed that after carcass deposition, the typical semi-arid soil community (e.g. Frankiales and Rhizobiales species) becomes temporarily dominated by the orders Bacillales and Pseudomonadales, known to contain plant growth-promoting species.
Our work indicates that complementing DNA based approaches with cultivation may give a more complete picture of the ecology of spore forming pathogens. Furthermore, the results suggests that the increased vegetation biomass production found at carcass sites is due to both added nutrients and the proliferation of microbial taxa that can be beneficial for plant growth. Thus, future B. anthracis transmission events at carcass sites may be indirectly facilitated by the recruitment of plant-beneficial bacteria.
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