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Epidemiology and ecology of Bacillus cereus biovar anthracis: A project to build capacities for the detection and investigation of novel pathogens

Applicant Dr. Silke Klee
Subject Area Parasitology and Biology of Tropical Infectious Disease Pathogens
Term from 2016 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 299339077
 
Final Report Year 2023

Final Report Abstract

Since the discovery of Bcbva in African rainforest areas, this pathogen has been suspected to be a zoonotic agent of public health relevance. We have put considerable efforts in developing molecular and serological tools to allow us to answer the crucial question of its impact on human and animal health. We identified the Bcbva-specific seromarker pXO2-60 which we used in extensive seroprevalence studies where we could show that the frequency of exposure increases at proximity of rainforest habitats where wildlife is still present, in good agreement with expectations regarding a wildlife-borne pathogen. Thus far, and despite the implementation of specific surveillance in medical settings, we did not identify clinical cases caused by Bcbva. Yet, we have accumulated lots of evidence suggesting that this bacterium is highly virulent in all exposed mammal species in the wild but also in small animal models upon experimental infection, clearly indicating that human exposure likely translates into a life-threatening hazard. Therefore, there is little doubt that Bcbva has an impact on human health: this pathogen only passed unnoticed until now as a result of its unexpected nature and its occurrence in resource-poor countries. Our work contributed to changing this situation in Côte d’Ivoire (CIV), where Bcbva diagnostic tests are now routinely implemented in several national institutions in charge of human and animal health. A better understanding of the risks posed by Bcbva largely depends on a better characterization of its host range and geographic distribution, that is, a better understanding of its epidemiology and ecology in nature. Carcass monitoring in sub-Saharan Africa confirmed occurrence of Bcbva in the Taï National Park (TNP) of CIV and in rain forest areas of Cameroon, Central African Republic (RCA) and Democratic Republic of Congo (DRC). Bcbva affected ten mammal species of TNP (chimpanzees, six monkey species, duikers, mongooses and porcupines), gorillas in Cameroon and RCA, an elephant in RCA and a goat in DRC. The innovative use of flies as samplers of mammal DNA and bacteria showed presence of Bcbva in Liberia (in a region in proximity to TNP) and an even broader range of affected mammal species. Bcbva detection rate seems to fluctuate seasonally, peaking during the dry season, and it is also higher where mammal density is higher. Using Bcbva isolates from carcasses, bones and carrion flies collected between 1996 and 2014 in TNP, we were able to assemble 178 Bcbva genomes, revealing a high local genomic diversity, particularly when compared to what has been observed elsewhere for Ba. The high genetic diversity is consistent with extensive Bcbva activity and suggests that this pathogen did not emerge recently. Genome data indicated spatially restricted transmission which might reflect carcass-mediated spread of Bcbva. On the ground, carcass-deposition sites are likely to be the source of Bcbva infections, similar to what is known for Ba infection of grazing ungulates or scavengers. Flies and other arthropods (e.g. termites) may contribute to Bcbva transmission in the upper layers of the rainforest where strictly arboreal monkeys could be infected by direct intake of arthropods or by fruits or leaves contaminated with fly excretions. The oral infective dose is not known, and it is still unclear whether Bcbva would have to multiply in the arthropod gut or on the plant material to be able to initiate an infection. Pathogenicity, especially gene regulation, is dependent on the global regulator AtxA both in Bcbva and Ba. However, comparative transcriptomics and proteomics revealed a number of potential virulence factors (e. g. ABC transporters) which are differentially expressed under host-mimicking conditions. Their role in pathogenicity must be examined in further studies. Through full genome analyses of Bcbva strains sampled in CIV, Cameroon, CAR and DRC, we found a separate clade within the B. cereus group, distinct from the Ba clade. All strains are characterized by the presence of five genomic islands, the same mutation in the gene for the regulator PlcR, and the ability to synthesize a hyaluronic acid capsule and the Bcbva-specific antigen pXO2-60. The corresponding genes are plasmid-encoded and possess mutations in classic Ba strains, which exclude these strains as plasmid donors for Bcbva. Despite extensive sampling efforts, relatives of Bcbva which might have served as plasmid donors or recipients remain to be detected.

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