Modulation of eukaryotic cell apoptosis by members of the bacterial order Actinomycetales

Barry, Daniel P.; Beaman, Blaine L.

doi:10.1007/s10495-006-9236-3

Cited by 14 publications

(11 citation statements)

References 103 publications

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“…The induction of host cell apoptosis in response to a bacterial pathogen can be considered from two perspectives: as a virulence mechanism of the pathogen or as a defence mechanism of the host55. Most research indicates that the apoptosis of macrophages infected with mycobacteria functions as a host defence mechanism to eliminate the bacteria.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth

Lee

Whang

Choi

et al. 2016

Sci Rep

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Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis. Enhanced reactive oxygen species production and JNK activation were essential for MAV2054-mediated apoptosis and MAV2054-induced interleukin-6, tumour necrosis factor, and monocyte chemoattractant protein-1 production. MAV2054 was targeted to the mitochondrial compartment of macrophages treated with MAV2054 and infected with M. avium. Dissipation of the mitochondrial transmembrane potential (ΔΨm) and depletion of cytochrome c also occurred in MAV2054-treated macrophages. Apoptotic response, reactive oxygen species production, and ΔΨm collapse were significantly increased in bone marrow-derived macrophages infected with Mycobacterium smegmatis expressing MAV2054, compared to that in M. smegmatis control. Furthermore, MAV2054 expression suppressed intracellular growth of M. smegmatis and increased the survival rate of M. smegmatis-infected mice. Thus, MAV2054 induces apoptosis via a mitochondrial pathway in macrophages, which may be an innate cellular response to limit intracellular M. avium multiplication.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth

Lee

Whang

Choi

et al. 2016

Sci Rep

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“…Follow-up studies showed that N. asteroides strain GUH-2 was neuroinvasive in the brains of mice [44], [45] and monkeys [46] and that infection resulted in apoptotic death of DA neurons associated with proteasome inhibition [47], [48]. Another nocardial strain (GAM-5) has also been shown to induce impaired movements and similar pathological features in mice following sublethal infection [49].…”

Section: Discussionmentioning

confidence: 99%

Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration

et al. 2009

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Parkinson disease (PD) involves progressive neurodegeneration, including loss of dopamine (DA) neurons from the substantia nigra. Select genes associated with rare familial forms of PD function in cellular pathways, such as the ubiquitin-proteasome system (UPS), involved in protein degradation. The misfolding and accumulation of proteins, such as α-synuclein, into inclusions termed Lewy Bodies represents a clinical hallmark of PD. Given the predominance of sporadic PD among patient populations, environmental toxins may induce the disease, although their nature is largely unknown. Thus, an unmet challenge surrounds the discovery of causal or contributory neurotoxic factors that could account for the prevalence of sporadic PD. Bacteria within the order Actinomycetales are renowned for their robust production of secondary metabolites and might represent unidentified sources of environmental exposures. Among these, the aerobic genera, Streptomyces, produce natural proteasome inhibitors that block protein degradation and may potentially damage DA neurons. Here we demonstrate that a metabolite produced by a common soil bacterium, S. venezuelae, caused DA neurodegeneration in the nematode, Caenorhabditis elegans, which increased as animals aged. This metabolite, which disrupts UPS function, caused gradual degeneration of all neuronal classes examined, however DA neurons were particularly vulnerable to exposure. The presence of DA exacerbated toxicity because neurodegeneration was attenuated in mutant nematodes depleted for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA production. Strikingly, this factor caused dose-dependent death of human SH-SY5Y neuroblastoma cells, a dopaminergic line. Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule. Evidence of a robust neurotoxic factor that selectively impacts neuronal survival in a progressive yet moderate manner is consistent with the etiology of age-associated neurodegenerative diseases. Collectively, these data suggest the potential for exposures to the metabolites of specific common soil bacteria to possibly represent a contributory environmental component to PD.

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“…These phenotypes are capable of undergoing dedifferentiation, transdifferentiation, and apoptosis depending on the stimulus (Barry & Beaman 2006). These changes are orchestrated by a range of neurons and cytokines secreted into the damaged environment and SC autocrine factors.…”

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confidence: 99%

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Silva¹,

Silva²,

Baruque³

et al. 2008

Mem. Inst. Oswaldo Cruz

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Modulation of eukaryotic cell apoptosis by members of the bacterial order Actinomycetales

Cited by 14 publications

References 103 publications

Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth

Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth

Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

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