Virulence test using nematodes to prescreenNocardiaspecies capable of inducing neurodegeneration and behavioral disorders

Abstract

BackgroundParkinson’s disease (PD) is a disorder characterized by dopaminergic neuron programmed cell death. The etiology of PD remains uncertain—some cases are due to selected genes associated with familial heredity, others are due to environmental exposure to toxic components, but over 90% of cases have a sporadic origin.Nocardiaare Actinobacteria that can cause human diseases like nocardiosis. This illness can lead to lung infection or central nervous system (CNS) invasion in both immunocompromised and immunocompetent individuals. The main species involved in CNS areN. farcinica, N. nova,N. brasiliensisandN. cyriacigeorgica. Some studies have highlighted the ability ofN. cyriacigeorgicato induce Parkinson’s disease-like symptoms in animals. Actinobacteria are known to produce a large variety of secondary metabolites, some of which can be neurotoxic. We hypothesized that neurotoxic secondary metabolite production and the onset of PD-like symptoms in animals could be linked.MethodsHere we used a method to screen bacteria that could induce dopaminergic neurodegeneration before performing mouse experiments.ResultsThe nematodeCaenorhabditis elegansallowed us to demonstrate thatNocardiastrains belonging toN. cyriacigeorgicaandN. farcinicaspecies can induce dopaminergic neurodegeneration. Strains of interest involved with the nematodes in neurodegenerative disorders were then injected in mice. Infected mice had behavioral disorders that may be related to neuronal damage, thus confirming the ability ofNocardiastrains to induce neurodegeneration. These behavioral disorders were induced byN. cyriacigeorgicaspecies (N. cyriacigeorgicaGUH-2 andN. cyriacigeorgica44484) andN. farcinica10152.DiscussionWe conclude thatC. elegansis a good model for detectingNocardiastrains involved in neurodegeneration. This model allowed us to detect bacteria with high neurodegenerative effects and which should be studied in mice to characterize the induced behavioral disorders and bacterial dissemination.