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Blaine L. Beaman - One of the best experts on this subject based on the ideXlab platform.
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Nocardia asteroides strain guh 2 induces proteasome inhibition and apoptotic death of cultured cells
Research in Microbiology, 2007Co-Authors: Daniel P Barry, Blaine L. BeamanAbstract:Many bacterial pathogens have the ability to induce apoptosis in their hosts. It was previously shown that Nocardia asteroides strain GUH-2, a Gram-positive facultatively intracellular pathogen, is capable of inducing the apoptotic death of dopaminergic cells in the murine brain and in PC12 cells, a rat cell line. In this study, the apoptosis-inducing potential of N. asteroides GUH-2 was further explored using HeLa cells, a human epithelial cell line. HeLa cells were incubated for 5 hours with live Nocardiae, heat-killed bacteria, or unconcentrated Nocardial culture filtrate, and changes to the cells were monitored. Consistent with the previous studies, N. asteroides GUH-2 induced DNA fragmentation and apoptosis in HeLa cells. Caspase activation and disruption of the mitochondrial membrane potential were also investigated to determine their roles in the induction of cell death. In all these experiments, significant changes were only induced by live Nocardiae. A recent publication demonstrated that systemic administration of proteasome inhibitors can induce a Parkinsonian syndrome in rats that includes intraneuronal inclusions and characteristic behavioral alterations. Similar effects have been observed in mice and monkeys infected with N. asteroides GUH-2. In addition, some reports have shown that proteasome inhibition causes apoptotic death of affected cells. We therefore investigated the ability of N. asteroides GUH-2 to inhibit proteasome activity. Proteasome activity was significantly reduced, suggesting that this mechanism may be involved in the induction of apoptosis by these bacteria.
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comparison of pcr and culture for detection of Nocardia asteroides in brain specimens from experimentally infected balb c mice
Microbiological Research, 2004Co-Authors: David A Loeffler, Blaine L. Beaman, Dianne M Camp, Peter A Lewitt, Lihua Qu Nichols, Saipiroon MaksaereekulAbstract:Systemic infection of BALB/c mice with Nocardia asteroides strain GUH-2 results in widespread replication of the organism in the brain, followed by its immune-mediated clearance. The present study compared the sensitivity of polymerase chain reaction (PCR) to bacterial culture for detection of cerebral Nocardial infection in this experimental system. Mice (n=4/time point) were administered N. asteroides by intravenous injection, and brain specimens were evaluated for Nocardia by PCR and culture at post-infection days 2, 7, 14 and 21. Nocardia was detected by PCR in all infected animals on post-infection days 2, 7, and 14, and in one of four mice on post-infection day 21; in contrast, the organism was detected by culture only on post-infection days 2 and 7. These findings suggest that PCR may be more sensitive than culture for the detection of low numbers of Nocardia in the brain.
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Nocardia asteroides culture filtrates cause dopamine depletion and cytotoxicity in pc12 cells
Neurochemical Research, 2003Co-Authors: Dianne M Camp, Blaine L. Beaman, David A Loeffler, Bnan A Razoky, Stanley Tam, Peter A LewittAbstract:Experimental infection of BALB/c mice with the gram-positive bacterium Nocardia asteroides produces marked loss of nigrostriatal dopamine neurons, resulting in striatal dopamine depletion. To investigate the mechanism(s) responsible for this neuronal loss, we evaluated the influence of N. asteroides cell-free culture filtrates on rat pheochromocytoma PC12 cells, an in vitro model for dopamine neurons. Changes in cell viability and cell numbers were minimal after 24 h, but increased with longer incubation. In contrast, dopamine depletion occurred after 30 min incubation, and was greater with GUH-2 filtrate than with filtrate from the less virulent strain 10905. Incubation with the culture filtrate decreased viability in neuroblastoma and glioma cell lines, indicating that cytotoxic effects were not limited to dopaminergic cells. These findings suggest that the loss of nigrostriatal dopamine neurons and concomitant striatal dopamine depletion in Nocardia-infected mice may be due, at least in part, to the neurotoxicity of Nocardial secretory products.
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neuroinvasive Nocardia asteroides guh 2 induces apoptosis in the substantia nigra in vivo and dopaminergic cells in vitro
Experimental Neurology, 2002Co-Authors: Stanley Tam, L Beaman, Daniel P Barry, Blaine L. BeamanAbstract:Neurodegenerative diseases such as Parkinson's disease are increasingly prevalent in the aging population worldwide. The causes of these disorders are unknown, but many studies have suggested that the etiology is likely multifactorial and may involve exposure to something in the environment combined with the normal aging process. Nocardia asteroides are bacteria commonly found in the soil, and neuroinvasive strains of Nocardiae have been described. N. asteroides strain GUH-2 invades the brains of experimentally infected animals and selectively affects dopaminergic neurons of the substantia nigra (SN), causing an L-DOPA-responsive movement disorder resembling parkinsonism. Furthermore, dopaminergic neurons undergo morphological changes characteristic of apoptosis following Nocardial infection. Apoptosis has been implicated in dopaminergic neuronal dropout in Parkinson's patients as well as other parkinsonian models. Thus, in this study, in vivo and in vitro models were utilized to measure the ability of GUH-2 to induce the apoptotic death of dopaminergic cells. Following infection with GUH-2, dopaminergic apoptotic cells were identified in the SN of animals by in situ end labeling, which detects DNA fragmentation, combined with fluorescent immunolabeling of tyrosine hydroxylase-positive cells. In addition, apoptosis was observed in PC12 cell cultures incubated with GUH-2 by both in situ end labeling and the annexin V assay, which detects externalization of phosphatidylserine of the plasma membrane, indicating apoptotic death. Based on the results of these studies, it appears that experimental infection with N. asteroides provides a general model for studying apoptosis in parkinsonian disorders.
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bacterial clearance and survival are dependent on cxc chemokine receptor 2 ligands in a murine model of pulmonary Nocardia asteroides infection
Journal of Immunology, 2000Co-Authors: Thomas A Moore, Blaine L. Beaman, Robert M. Strieter, Michael W Newstead, Borna Mehrad, Theodore J. StandifordAbstract:Survival from murine pulmonary nocardiosis is highly dependent on CXC chemokine receptor-2 (CXCR2) ligand-mediated neutrophil chemotaxis and subsequent clearance of the infectious agent Nocardia asteroides. Intratracheal inoculation of N. asteroides rapidly up-regulated the CXC chemokines macrophage inflammatory protein-2 (MIP-2) and KC within 24 h, with levels remaining elevated through day 3 before returning to near baseline levels by day 7. Coinciding with elevated MIP-2 and KC were the rapid recruitment of neutrophils and clearance of the organism. Anti-Ly-6G Ab-mediated neutrophil depletion before bacterial challenge resulted in strikingly increased mortality to N. asteroides infection. The relative contribution of MIP-2 in neutrophil recruitment was examined by anti-MIP-2 Ab treatment before Nocardial infection. MIP-2 neutralization had no detrimental effects on survival, neutrophil recruitment, or bacterial clearance, suggesting the usage of additional or alternative CXCR2-binding ligands. The importance of the CXC family of chemokines was determined by the administration of an anti-CXCR2 Ab capable of blocking ligand binding in vivo. Anti-CXCR2 treatment greatly increased mortality by preventing neutrophil migration into the lung. Paralleling this impaired neutrophil recruitment was a 100-fold increase in lung bacterial burden. Combined, these observations indicate a critical role for neutrophils and CXC chemokines during Nocardial pneumonia. These data directly link CXCR2 ligands and neutrophil recruitment and lend further support to the concept of CXC chemokine redundancy. For infections highly dependent on neutrophils, such as Nocardial pneumonia, this is of critical importance.
L Beaman - One of the best experts on this subject based on the ideXlab platform.
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neuroinvasive Nocardia asteroides guh 2 induces apoptosis in the substantia nigra in vivo and dopaminergic cells in vitro
Experimental Neurology, 2002Co-Authors: Stanley Tam, L Beaman, Daniel P Barry, Blaine L. BeamanAbstract:Neurodegenerative diseases such as Parkinson's disease are increasingly prevalent in the aging population worldwide. The causes of these disorders are unknown, but many studies have suggested that the etiology is likely multifactorial and may involve exposure to something in the environment combined with the normal aging process. Nocardia asteroides are bacteria commonly found in the soil, and neuroinvasive strains of Nocardiae have been described. N. asteroides strain GUH-2 invades the brains of experimentally infected animals and selectively affects dopaminergic neurons of the substantia nigra (SN), causing an L-DOPA-responsive movement disorder resembling parkinsonism. Furthermore, dopaminergic neurons undergo morphological changes characteristic of apoptosis following Nocardial infection. Apoptosis has been implicated in dopaminergic neuronal dropout in Parkinson's patients as well as other parkinsonian models. Thus, in this study, in vivo and in vitro models were utilized to measure the ability of GUH-2 to induce the apoptotic death of dopaminergic cells. Following infection with GUH-2, dopaminergic apoptotic cells were identified in the SN of animals by in situ end labeling, which detects DNA fragmentation, combined with fluorescent immunolabeling of tyrosine hydroxylase-positive cells. In addition, apoptosis was observed in PC12 cell cultures incubated with GUH-2 by both in situ end labeling and the annexin V assay, which detects externalization of phosphatidylserine of the plasma membrane, indicating apoptotic death. Based on the results of these studies, it appears that experimental infection with N. asteroides provides a general model for studying apoptosis in parkinsonian disorders.
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differences in the interactions of Nocardia asteroides with macrophage endothelial and astrocytoma cell lines
Infection and Immunity, 1994Co-Authors: L Beaman, B L BeamanAbstract:An in vitro model for studying host cell interactions with Nocardia asteroides was developed. Thus, macrophage cell lines J774A.1 and P388D1, pulmonary artery endothelium cell line CPAE, rat glial tumor cell line C6, and human astrocytoma cell lines CCF-STTG1 and U-373 MG were infected with either log- or stationary-phase cells of N. asteroides GUH-2, and the host cell-Nocardia interactions were determined by light microscopy and electron microscopy. Polyclonal antiNocardial antibody did not enhance uptake of Nocardiae by any of these cell lines; however, log-phase cells of GUH-2 infected a higher percentage of J774A.1 and P388D1 than did stationary-phase organisms. When cells infected with stationary-phase GUH-2 were incubated for 6 h, filaments developed, which indicated that Nocardial growth had occurred. In J774A.1 and P388D1, only 31 to 57% of the total stationary-phase coccobacillary cells that were phagocytized formed filaments within 6 h. This indicated that there was some inhibition of growth of the phagocytized Nocardiae within these macrophage cell lines; however, the Nocardiae grew within the endothelial (> 87% filaments) and astrocytoma (100% filaments) cell lines. Microfilament inhibitor cytochalasin B inhibited uptake of GUH-2 by macrophages and other cell lines, except that there was no effect on uptake of Nocardial cells by astrocytoma cell line U-373 MG. Scanning and transmission electron microscopy showed phagocytosis of GUH-2 by the different cell lines. In cytochalasin B-treated cells, Nocardiae were shown to penetrate through the cell surface and become internalized in a manner distinct from typical phagocytosis, suggesting that filamentous forms of this organism have a phagocytosis-independent invasion factor. The extent of this cytochalasin-resistant cellular penetration by the Nocardiae differed in the different cell lines.
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Nocardia species host parasite relationships
Clinical Microbiology Reviews, 1994Co-Authors: B L Beaman, L BeamanAbstract:The Nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to Nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the Nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of Nocardiae in neurodegenerative diseases in humans needs to be investigated. Images
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Nocardia species host parasite relationships
Clinical Microbiology Reviews, 1994Co-Authors: B L Beaman, L BeamanAbstract:The Nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to Nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the Nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of Nocardiae in neurodegenerative diseases in humans needs to be investigated.
Michael Goodfellow - One of the best experts on this subject based on the ideXlab platform.
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molecular fingerprinting of some clinically significant Nocardia and related strains by restriction polymorphism ribosomal rna analyses
Turkish Journal of Biology, 2010Co-Authors: Kamil Işik, Michael GoodfellowAbstract:Fifty-three Nocardia strains were the subject of a restriction polymorphic ribosomal RNA analysis (ribotyping) designed to distinguish between representatives of clinically significant species and related strains. The organisms were assigned to 19 groups using a combination of EcoRV gene restriction endonuclease patterns and a digoxigenin-labelled Streptomyces violaceoruber TK21 rDNA probe. Each ribotype group contained 4 to 13 restriction fragments that ranged in size from 20.7 to 0.9 kb. The N. brasiliensis, N. crassostreae, N. farcinica, N. otitidiscaviarum, and N. seriolea strains showed distinct ribotype patterns. Unique banding patterns were also seen for the type strains of N. brevicatena, N. carnea, N. salmonicida, N. uniformis, and N. vaccinii, and for the single representatives of "N. fusca", "N. pseudosporangifera", and "N. violaceofusca". More than one banding pattern was detected for the N. asteroides, N. flavorosea, N. nova, N. pseudobrasiliensis, and N. transvalensis strains. The results are in line with current trends in Nocardial systematics thereby indicating that restriction polymorphism ribosomal RNA analyses provide valuable data for the classification and identification of novel and pathogenic Nocardiae at the species level.
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Nocardia pigrifrangens sp nov a novel actinomycete isolated from a contaminated agar plate
International Journal of Systematic and Evolutionary Microbiology, 2004Co-Authors: Liming Wang, Yamei Zhang, Ying Huang, Luis A Maldonado, Zhiheng Liu, Michael GoodfellowAbstract:A polyphasic study was undertaken to establish the taxonomic position of an actinomycete strain isolated from a contaminated agar plate. The strain, designated 7031T, had morphological and chemotaxonomic properties typical of the genus Nocardia. An almost-complete 16S rRNA gene sequence determined for the strain was aligned with available sequences for Nocardiae, and phylogenetic trees were inferred using three tree-generating algorithms. Strain 7031T clustered with the type strains of Nocardia carnea and Nocardia flavorosea, showing low 16S rRNA gene sequence similarities to these species (97·2 and 97·5 %, respectively). The strain was also distinguished from the closest species by a range of phenotypic properties. It is proposed that the strain be recognized as a novel species of Nocardia, Nocardia pigrifrangens sp. nov., the type strain of which is 7031T (=AS 4.1808T=JCM 11884T).
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Nocardia africana sp nov a new pathogen isolated from patients with pulmonary infections
Journal of Clinical Microbiology, 2001Co-Authors: Luis A Maldonado, Mohamed E Hamid, Ghada Sharaf S Eldin, Maha F Mohamed, Nageeb S Saeed, Michael GoodfellowAbstract:Eight actinomycete strains, isolated from 8 out of 400 sputum samples examined, taken from patients with pulmonary diseases at the Chest Unit of Khartoum Teaching Hospital in the Sudan, were provisionally assigned to the genus Nocardia according to morphological criteria. These isolates were studied further in order to establish their taxonomic status. They were found to have morphological and chemical properties typical of Nocardiae and formed a monophyletic clade in the 16S ribosomal DNA tree together with Nocardia vaccinii. The strains showed a unique pattern of phenotypic properties that distinguished them from representatives of recognized Nocardia species, including Nocardia vaccinii. The strains were considered to merit species status and were designated Nocardia africana sp. nov. The findings of the present study are consistent with the view that pulmonary nocardiosis may occur in a substantial proportion of patients who exhibit chronic lung diseases in African countries. It is important, therefore, that clinicians in such countries consider this condition, especially when patients with respiratory infections fail to respond to antitubercular therapy.
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Nocardia, nocardiosis and mycetoma.
Medical Mycology, 1998Co-Authors: Patrick Boiron, S A Gumaa, K Isik, M M Mcneil, Mario C. Salinas-carmona, Romano Locci, Michael Goodfellow, Hasan ShojaeiAbstract:Abstract The recent emergence of invasive infections due to Nocardia spp., including nosocomial outbreak, is now evident. Newer molecular diagnostic and typing methods are developed. Although sulfonamide-based therapy is generally effective, optimal treatment may be guided by antimicrobial susceptibility testing of isolates. The improved classification of Nocardiae and other related genera such as actinomadurae, using the 16S ribosomal RNA sequencing, provide a sound basis for improved diagnostic methods for the identification of members of clinically significant species. The commonest cause of eumycetoma in Sudan is Madurella mycetomatis, and Streptomyces somaliensis and Actinomadura madurae for actinomycetoma. The humoral immunity response in actinomycetoma patients and in experimental mice was measured and significant titre of anti-P24 antibody was demonstrated.
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a phylogenetic analysis of the genus Nocardia with 16s rrna gene sequences
International Journal of Systematic and Evolutionary Microbiology, 1995Co-Authors: Jongsik Chun, Michael GoodfellowAbstract:Partial sequences of the 16S rRNA genes of the type strains of nine species of the genus Nocardia were determined following the isolation and cloning of the amplified genes. These sequences were aligned with the sequences of representatives of the genera Corynebacterium, Gordona, Mycobacterium, Rhodococcus, and Tsukamurella, and phylogenetic trees were inferred by using the Fitch-Margoliash and neighbor-joining methods. The genus Nocardia formed a distinct clade that was most closely associated with the genus Rhodococcus. The average level of sequence similarity found among the type strains of the Nocardia species was 97.2 ± 0.7%. Two sublines were recognized within the Nocardia clade; one encompassed Nocardia asteroides and related species, and the other encompassed Nocardia otitidiscaviarum and allied taxa. Separation of the two sublines is based on differences in helix 37–1. The results of isoprenoid quinone analyses provided evidence that Nocardiae can be distinguished from all other actinomycete taxa on the basis of their characteristic menaquinone profiles. Nocardiae typically contain hexahydrogenated menaquinones with eight isoprene units in which the two end units are cyclized.
B L Beaman - One of the best experts on this subject based on the ideXlab platform.
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University Schools of Medicine and Dentistry,
2016Co-Authors: B L Beaman, J. Burnside, B. Edwards, W. CauseyAbstract:A survey of members of the Infectious Diseases Society of America indicated that Nocardial infections are not rare. Probably between 500 and 1,000 cases are recognized in the United States each year, of which 85 % are serious pulmonary or systemic infections. Although Nocardial infections are usually opportunistic infections in the compromised host, at least 15 % of the infections in this series occurred in patients without a definable predisposing condition. Nocardial infec-tions occurred in a random geographic distribution within this country, with affected males outnumbering females by 3: 1. Most patients were between the ages of 21 and 50 years; however, the age range was broad. The number and variety of infections caused by Nocardia species other than Nocardia asteroides have been underestimated. Between 8.6 % and 18.8 % of pulmonary-systemic infec-tions in this series were caused by species of Nocardia other than N. asteroides. Nacardia was first recognized as a pathogen by Nocard in 1888, when he isolated an agent from lesions of a peculiar granulomatous disease o
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differences in the interactions of Nocardia asteroides with macrophage endothelial and astrocytoma cell lines
Infection and Immunity, 1994Co-Authors: L Beaman, B L BeamanAbstract:An in vitro model for studying host cell interactions with Nocardia asteroides was developed. Thus, macrophage cell lines J774A.1 and P388D1, pulmonary artery endothelium cell line CPAE, rat glial tumor cell line C6, and human astrocytoma cell lines CCF-STTG1 and U-373 MG were infected with either log- or stationary-phase cells of N. asteroides GUH-2, and the host cell-Nocardia interactions were determined by light microscopy and electron microscopy. Polyclonal antiNocardial antibody did not enhance uptake of Nocardiae by any of these cell lines; however, log-phase cells of GUH-2 infected a higher percentage of J774A.1 and P388D1 than did stationary-phase organisms. When cells infected with stationary-phase GUH-2 were incubated for 6 h, filaments developed, which indicated that Nocardial growth had occurred. In J774A.1 and P388D1, only 31 to 57% of the total stationary-phase coccobacillary cells that were phagocytized formed filaments within 6 h. This indicated that there was some inhibition of growth of the phagocytized Nocardiae within these macrophage cell lines; however, the Nocardiae grew within the endothelial (> 87% filaments) and astrocytoma (100% filaments) cell lines. Microfilament inhibitor cytochalasin B inhibited uptake of GUH-2 by macrophages and other cell lines, except that there was no effect on uptake of Nocardial cells by astrocytoma cell line U-373 MG. Scanning and transmission electron microscopy showed phagocytosis of GUH-2 by the different cell lines. In cytochalasin B-treated cells, Nocardiae were shown to penetrate through the cell surface and become internalized in a manner distinct from typical phagocytosis, suggesting that filamentous forms of this organism have a phagocytosis-independent invasion factor. The extent of this cytochalasin-resistant cellular penetration by the Nocardiae differed in the different cell lines.
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Nocardia species host parasite relationships
Clinical Microbiology Reviews, 1994Co-Authors: B L Beaman, L BeamanAbstract:The Nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to Nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the Nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of Nocardiae in neurodegenerative diseases in humans needs to be investigated. Images
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Nocardia species host parasite relationships
Clinical Microbiology Reviews, 1994Co-Authors: B L Beaman, L BeamanAbstract:The Nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to Nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the Nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of Nocardiae in neurodegenerative diseases in humans needs to be investigated.
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l dopa responsive movement disorder caused by Nocardia asteroides localized in the brains of mice
Infection and Immunity, 1991Co-Authors: S Kohbata, B L BeamanAbstract:Nocardia asteroides can cause infections in the brain of humans and a variety of animals. In mice, invasion of the central nervous system results in specific neurologic signs. Following intravenous injection of various doses of log-phase N. asteroides GUH-2 into female BALB/c mice, localization and growth of Nocardial cells within the brains were determined, histopathological sections were prepared, and Nissl substance and tyrosine hydroxylase immunoreactivity were observed. Mice were monitored for the development of neurologic signs, and their responsiveness to L-dopa was determined. It was shown that Nocardial cells became localized within specific regions of the brain and then underwent rapid growth followed by a delayed clearance, and there was no inflammatory response at the site of invasion for 24 h. Mice that received a subclinical dose of Nocardiae developed specific neurologic signs that emerged following the elimination of Nocardial cells from the brain. On the basis of the specific signs, mice could be divided into distinct groups. One group consisted of animals that had a form of hemiparesis that did not respond to L-dopa. They expressed a deviation of the head and a tendency to roll, and when suspended by the tail they would spin rapidly. The second group of mice developed a rhythmic, uncontrolled vertical shake of the head (four to five times per s) tremulous movement, stooped posture, restlessness, and no signs of hemiparesis. The head shakes were temporarily stopped by treatment with L-dopa. Mice that expressed head shakes had a loss of Nissl substance and tyrosine hydroxylase immunoreactivity in the neurons of the substantia nigra and ventral tegmental areas of the brain. Hyaline inclusion bodies that resembled Lewy bodies were found in the neurons of mice with head shake 1 month after infection. Therefore, mice infected with N. asteroides may serve as a model for studying parkinsonian signs and other degenerative diseases involving extrapyramidal and pyramidal systems.
Patrick Boiron - One of the best experts on this subject based on the ideXlab platform.
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nocardiosis in a teaching hospital in the central anatolia region of turkey treatment and outcome
Clinical Microbiology and Infection, 2005Co-Authors: Orhan Yildiz, Patrick Boiron, Emine Alp, Bulent Tokgoz, Bulent Tucer, Bilgehan Aygen, Bulent Sumerkan, Andree Couble, Mehmet DoganayAbstract:Predisposing factors, antimicrobial susceptibility patterns, treatment and outcome were analysed for nine consecutive patients with nocardiosis. Predisposing factors were identified in six (67%) of the nine patients. Clinical syndromes of Nocardial infection were pulmonary infection (three patients), cerebral infection (five patients) and disseminated infection (one patient). The predominant (60%) species was Nocardia farcinica rather than the Nocardia asteroides complex. Treatment was started empirically, modified according to the antimicrobial susceptibility pattern, and then continued for 6-12 months. Overall mortality was 33%, with death being caused by the Nocardia infection in two cases.
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report of human nocardiosis in italy between 1993 and 1997
European Journal of Epidemiology, 2001Co-Authors: Claudio Farina, Patrick Boiron, I Ferrari, F Provost, Antonio GoglioAbstract:During a 5-year period, from 1993 to 1997, Nocardial infection was diagnosed in 26 patients admitted to hospitals in 11 cities in Italy. Pathogens were identified as Nocardia asteroides in 18 cases, as N. farcinica in five cases, as N. nova in two and as N. brasiliensis in one case. All cases were difficult to diagnose, as usually it happens with this disease: physicians have to be alert to suspect Nocardial infection so that appropriate therapy can be early given. This is the second retrospective report on Nocardia spp. infection conducted in Italy, suggesting the utility to organise a permanent network for a national survey system for nocardiosis.
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Nocardia, nocardiosis and mycetoma.
Medical Mycology, 1998Co-Authors: Patrick Boiron, S A Gumaa, K Isik, M M Mcneil, Mario C. Salinas-carmona, Romano Locci, Michael Goodfellow, Hasan ShojaeiAbstract:Abstract The recent emergence of invasive infections due to Nocardia spp., including nosocomial outbreak, is now evident. Newer molecular diagnostic and typing methods are developed. Although sulfonamide-based therapy is generally effective, optimal treatment may be guided by antimicrobial susceptibility testing of isolates. The improved classification of Nocardiae and other related genera such as actinomadurae, using the 16S ribosomal RNA sequencing, provide a sound basis for improved diagnostic methods for the identification of members of clinically significant species. The commonest cause of eumycetoma in Sudan is Madurella mycetomatis, and Streptomyces somaliensis and Actinomadura madurae for actinomycetoma. The humoral immunity response in actinomycetoma patients and in experimental mice was measured and significant titre of anti-P24 antibody was demonstrated.
