Site-specific growth of Nocardia asteroides in the murine brain

Ogata, Sakae; Beaman, Blaine L.

doi:10.1128/iai.60.8.3262-3267.1992

Cited by 22 publications

(23 citation statements)

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“…Khobata & Beaman, 1991 reported that a sublethal injection of Nocardia cyriacigeorgica GUH-2 can induce a syndrome in mice which shares clinical and pathological similarities with PD. These results were confirmed in other studies (Khobata & Beaman, 1991;Ogata & Beaman, 1992).…”

Section: Introductionsupporting

confidence: 89%

Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders

Claire

Zoropogui

Voisin

et al. 2017

Preprint

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Background. Parkinson’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. Nocardia are 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 are N. farcinica, N. nova, N. brasiliensis and N. cyriacigeorgica. Some studies have highlighted the ability of N. cyriacigeorgica to 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. Methods. Here we used a method to screen bacteria that could induce dopaminergic neurodegeneration before performing mouse experiments. Results.The nematode Caenorhabditis elegans allowed us to demonstrate that Nocardia strains belonging to N. cyriacigeorgica and N. farcinica species 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 of Nocardia strains to induce neurodegeneration. These behavioral disorders were induced by N. cyriacigeorgica species (N. cyriacigeorgica GUH-2 and N. cyriacigeorgica 44484) and N. farcinica 10152. Discussion.We conclude that C. elegans is a good model for detecting Nocardia strains 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.

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Section: Introductionsupporting

confidence: 89%

Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders

Claire

Zoropogui

Voisin

et al. 2017

Preprint

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“…Also, N. asteroides GUH-2 metabolizes tyrosine to produce an iron-binding compound (19). Since glutamate, acid phosphatase, and tyrosine are important components in specific regions of the brain (20,21), the ability of GUH-2 to preferentially metabolize these compounds may be significant for its survival and preferential growth within neurons in regions such as the pons, substantia nigra, red nucleus, thalamus, and hypothalamus (18).…”

Section: Discussionmentioning

confidence: 99%

“…To facilitate visualization of the localized growth of the nocardiae in the brain, a lethal dose of 106 CFU per mouse (0.1 ml of the bacterial suspension) was injected into the tail vein. It was shown that, at this dose, approximately 800 to 1,000 CFU became localized within the brain 3 h after injection (16)(17)(18). Preparation of the infected brain for electron microscopy.…”

Section: Methodsmentioning

confidence: 99%

“…By using this murine model, it was shown that a nonlethal i.v. injection of GUH-2 resulted in a silent, self-limited invasion of the brain (16)(17)(18). Light microscopy of coronal sections of the infected brain suggested that the bacteria adhered to capillaries and that, by some mechanism, the organisms grew into the brain tissue without destroying the integrity of the blood-brain barrier (16).…”

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Ultrastructural analysis of growth of Nocardia asteroides during invasion of the murine brain

Beaman

1993

Infect Immun

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BALB/c mice were infected with 106 CFU of log-phase cells of Nocardia asteroides GUH-2 by tail vein injection (at this lethal inoculum dose, approximately 800 to 1,000 CFU becomes deposited in the brain). At 24 h after infection, the ultrastructural interactions of the nocardiae during growth within the murine brain were investigated. The nocardiae grew perivascularly in the pons, substantia nigra, hypothalamus, and thalamus portions of the brain, where they were either within or associated with most brain cell types. There appeared to be a propensity for growth within the soma of neurons and their axonal extensions. The nocardial cells were surrounded by 1 to 30 layers of membrane, and the innermost membrane was usually tightly adherent to the cell wall. This compartmentalization of nocardiae within brain cells could contribute to their failure to induce an inflammatory response or a cytopathic effect. Nevertheless, the bacteria were able to obtain adequate nutrients from the host to grow within the brain. The nocardiae were not completely inert, since some of the brain cells showed signs of degeneration. The myelin sheaths of axons were the most strongly affected, and there was evidence of demyelinization and axonal degeneration. Nocardiae growing within brain cells were

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“…277 indicate that the ability to induce neurodegeneration could be widely distributed in the Nocardia 278 genus. 279 280 Dopaminergic neuron neurodegeneration 281 The N. cyriacigeorgica GUH-2 strain can invade the neuronal central system and cause 282 dopaminergic neurodegeneration in mice (Ogata & Beaman, 1992). Here we demonstrate that 283 this property induced by N. cyriacigeorgica can be obtained using a rapid test with the C. 284 elegans BY250 vtIs7 [Pdat-1:GFP]) line.…”

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Supplemental Information 2: Number of Nematodes Affected in Their Movement Using the Touch Response Test

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Background. Parkinson'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. Nocardia are 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 are N. farcinica, N. nova, N. brasiliensis and N. cyriacigeorgica. Some studies have highlighted the ability of N.cyriacigeorgica to 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. Methods. Here we used a method to screen bacteria that could induce dopaminergic neurodegeneration before performing mouse experiments. Results.The nematode Caenorhabditis elegans allowed us to demonstrate that Nocardia strains belonging to N. cyriacigeorgica and N. farcinica species 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 of Nocardia strains to induce neurodegeneration. These behavioral disorders were induced by N. cyriacigeorgica species (N. cyriacigeorgica GUH-2 and N. cyriacigeorgica 44484) and N. farcinica 10152. Discussion.We conclude that C. elegans is a good model for detecting Nocardia strains involved in neurodegeneration. This model allowed us to detect bacteria PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.3152v1 | CC BY 4.0 Open Access | recwith high neurodegenerative effects and which should be studied in mice to characterize the induced behavioral disorders and bacterial dissemination. 1 Virulence test using nematodes to prescreen Nocardia species 2 capable of inducing neurodegeneration and behavioral disorders 3 4 Abstract 22 23 Background. Parkinson's disease (PD) is a disorder characterized by dopaminergic neuron 24 programmed cell death. The etiology of PD remains uncertain-some cases are due to selected 25 genes associated with familial heredity, others are due to environmental exposure to toxic 26 components, but over 90% of cases have a sporadic origin. Nocardia are Actinobacteria that can 27 cause human diseases like nocardiosis. This illness can lead to lung infection or central nervous 28 system (CNS) invasion in both immunocompromised and immunocompetent individuals. The 29 main species involved in CNS are N . farcinica, N. nova, N. brasiliensis and N. cyriacigeorgica. 30 Some studies have highlighted the ability of N. cyriacigeorgica to induce Parkinson's disease-31 like symptom...

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Site-specific growth of Nocardia asteroides in the murine brain

Cited by 22 publications

References 23 publications

Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders

Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders

Ultrastructural analysis of growth of Nocardia asteroides during invasion of the murine brain

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