Commentary: Advancement of Knowledge of Brucella Over the Past 50 Years

Brucella ceti, a cetacean and zoonotic pathogen displaying a marked neurotropism in striped dolphins (Stenella coeruleoalba), appears to be the ancestor and a close relative ofB. abortus, infecting cattle, as well as of B. melitensis, infecting sheep and goat (1). In addition to the elegant mechanisms and strategies utilized by Brucella genus members for entering and surviving into host cells, which are clearly explained in the aforementioned review article (2), the interaction between bacterial Hsp60 – amember of theGroEL family of chaperonins – and cellular prion protein (PrPC) has been reported to play a crucial role in B. abortus infection of murine, bone marrow-derived macrophages, with no evidence of microbial colonization and replication in cells from PrPC-deficient mice (3, 4). As “top predators,” cetaceans may accumulate within their tissues high concentrations of immunotoxic and neurotoxic “persistent organic pollutants” (POPs) like dioxins and dioxin-like compounds (DLCs) (5, 6), which have been demonstrated to exert pro-apoptotic activity on human neuronal cells (7). As a consequence, following dioxin-induced apoptosis, PrPC overexpression is likely to occur on host cell membrane, given the anti-apoptotic role of PrPC, which is consistently expressed on brain cells (8). Based upon the aforementioned model, the heavy (cerebral and extra-neural) tissue loads of lipophylic dioxins and DLCs commonly detected in stranded dolphins (5, 6) could elicit PrPC overexpression on behalf of brain cells, resulting at its turn in an amplified colonization and replication activity ofB. ceti inside these cells. The recently characterized expression patterns of PrPC within the cerebral parenchyma as well as in secondary lymphoid tissues from wild dolphins (9), which resemble those previously reported in terrestrial mammals (8), provide additional support for such hypothesis, thereby making biologically plausible the occurrence of “neurobrucellosis,” a neurological disease condition frequently observed in B. ceti-affected striped dolphins (1). Indeed, high levels of dioxins andDLCshave been recently found in tissues fromB. cetimeningoencephalitisaffected striped dolphins beached along the Ionian Sea coast of Italy (Antonio Petrella and Pasquale Troiano, personal communication). In this respect, it should be also emphasized that significant differences have been recently reported in the endo-cerebral expression levels of 5-lipoxygenase (5-LOX), a neurodegeneration biomarker (10), between infectious encephalitis/meningoencephalitis-affected and -unaffected striped dolphins, with the most consistent intensity of expression of the aforementioned enzyme having been detected in a B. ceti-infected individual (11). This appears to be a remarkable