Neuroinfectiology of an atypical anthrax-causing pathogen in wild chimpanzees

Abstract

Bacillus cereusbiovaranthracis(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, suggestsBcbvais zoonotic. While classicalB. anthracis-induced anthrax has been described to affect the central nervous system at a progressive disease-state, the neuroinfectiology ofBcbvais 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 thatBcbvainduced meningitis analogous toB. anthracis. Further, histological visualisation of bacteria and leukocytes in the subarachnoid space evidenced the bacterium’s capability to breach the arachnoid barrier.Bcbvawas 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 toB. anthracisthat 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 revealBcbva’s ability to breach blood-brain barriers which results in a pronounced neuropathogenicity.Bcbvacauses 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.