Neuroinfectiology of an atypical anthrax-causing pathogen in wild chimpanzees

Tobias Gräßle,Carsten Jäger,Evgeniya Kirilina,Jenny E. Jaffe, Penelope Carlier,Andrea Pizarro, Anna Jauch, Katja Reimann,Ilona Lipp, EBC consortium,Roman M. Wittig,Catherine Crockford,Nikolaus Weiskopf,Fabian H. Leendertz, Markus Morawski

biorxiv(2023)

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摘要
Bacillus cereus biovar anthracis ( Bcbva ) is an atypical anthrax-causing bacterium, inflicting wildlife fatalities across African rainforest ecosystems. The pathogen’s virulence in one of our closest living relatives, the chimpanzee, together with human serological evidence, suggests Bcbva is zoonotic. While classical B. anthracis -induced anthrax has been described to affect the central nervous system at a progressive disease-state, the neuroinfectiology of Bcbva is yet unknown. Here we characterised the pathogen’s neuro-invasiveness via gross pathological assessment, ultra-high resolution quantitative Magnetic Resonance Imaging and histological analysis on four brains, which were extracted from naturally deceased wild chimpanzees in Taï National Park, Côte d’Ivoire. Based on macroscopically evident pial vessel congestion and haemorrhages as well as cortical siderosis detected via MRI, we concluded that Bcbva induced meningitis analogous to B. anthracis . Further, histological visualisation of bacteria and leukocytes in the subarachnoid space evidenced the bacterium’s capability to breach the arachnoid barrier. Bcbva was detected in the brain parenchyma of all four cases. This indicates a higher ability to transgress the glia limitans and therefore exhibits a higher neuroinvasiveness compared to B. anthracis that predominantly stays confined to the meninges. Heightened glial fibrillary acidic protein (GFAP) expression but little morphological gliosis suggest a rapid disease progression leading to host-death within hours to a few days after central nervous system invasion. Overall our results reveal Bcbva ’s ability to breach blood-brain barriers which results in a pronounced neuropathogenicity. Bcbva causes extensive damage to the meninges and the brain parenchyma, as well as rapid and massive digestion of brain extracellular matrix in chimpanzees and potentially so in humans in case of zoonotic spillover. ### Competing Interest Statement The authors have declared no competing interest.
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