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排序方式: 共有238条查询结果,搜索用时 15 毫秒
61.
John Panepinto Kazimierz Komperda Susana Frases Yoon-Dong Park Julianne T. Djordjevic Arturo Casadevall Peter R. Williamson 《Molecular microbiology》2009,71(5):1165-1176
The cell wall of pathogenic fungi such as Cryptococcus neoformans , provides a formidable barrier to secrete virulence factors that produce host cell damage. To study secretion of virulence factors to the cell periphery, sec6 RNAi mutant strains of C. neoformans were tested for virulence factor expression. The studies reported here show that SEC6 RNAi mutant strains were defective in a number of virulence factors including laccase, urease as well as soluble polysaccharide and demonstrated attenuated virulence in mice. Further analysis by transmission electron microscopy detected the production of abundant extracellular exosomes in wild-type strains containing empty plasmid, but a complete absence in the i SEC6 strain. In addition, a green fluorescent protein–laccase fusion protein demonstrated aberrant localization within cytoplasmic vesicles in i SEC6 strains. In contrast, i SEC6 strains retained normal growth at 37°C, as well as substantially normal capsule formation, phospholipase activity and total secreted protein. These results provide the first molecular evidence for the existence of fungal exosomes and associate these vesicles with the virulence of C. neoformans . 相似文献
62.
Susana Frases Bruno Pontes Marcio L. Rodrigues Arturo Casadevall 《Biophysical journal》2009,97(4):937-945
Microbial capsules are important for virulence, but their architecture and physical properties are poorly understood. The human pathogenic fungus Cryptococcus neoformans has a large polysaccharide capsule that is necessary for virulence and is the target of protective antibody responses. To study the C. neoformans capsule we developed what we believe is a new approach whereby we probed the capsular elastic properties by applying forces using polystyrene beads manipulated with optical tweezers. This method allowed us to determine the Young's modulus for the capsule in various conditions that affect capsule growth. The results indicate that the Young's modulus of the capsule decreases with its size and increases with the Ca2+ concentration in solution. Also, capsular polysaccharide manifests an unexpected affinity for polystyrene beads, a property that may function in attachment to host cells and environmental structures. Bead probing with optical tweezers provides a new, nondestructive method that may have wide applicability for studying the effects of growth conditions, immune components, and drugs on capsular properties. 相似文献
63.
Allan Jefferson Guimarães Susana Frases Radamés J. B. Cordero Leonardo Nimrichter Arturo Casadevall Joshua D. Nosanchuk 《Cellular microbiology》2010,12(6):740-753
The polysaccharide capsule of the fungus Cryptococcus neoformans is its main virulence factor. In this study, we determined the effects of mannitol and glucose on the capsule and exopolysaccharide production. Growth in mannitol significantly increased capsular volume compared with cultivation in glucose. However, cells grown in glucose concentrations higher than 62.5 mM produced more exopolysaccharide than cells grown in mannitol. The fibre lengths and glycosyl composition of capsular polysaccharide from yeast grown in mannitol was structurally different from that of yeast grown in glucose. Furthermore, mannitol treatment of mice infected intratracheally with C. neoformans resulted in fungal cells with significantly larger capsules and the mice had reduced fungal dissemination to the brain. Our results demonstrate the capacity of carbohydrate source and concentration to modify the expression of a major virulence factor of C. neoformans. These findings may impact the clinical management of cryptococcosis. 相似文献
64.
65.
Cryptococcus neoformans capsular polysaccharide component galactoxylomannan induces apoptosis of human T-cells through activation of caspase-8 总被引:3,自引:0,他引:3
Pericolini E Cenci E Monari C De Jesus M Bistoni F Casadevall A Vecchiarelli A 《Cellular microbiology》2006,8(2):267-275
The major virulence factor of Cryptococcus neoformans is its polysaccharide capsule composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and mannoproteins. A variety of immunomodulating activities have been described for GXM and mannoproteins but little is known about possible interactions of GalXM with the immune system. In the present article, we investigate the effect of purified soluble GalXM on human T lymphocytes. The results indicate that, GalXM (i) can affect selected immune responses; (ii) causes significant impairment of T cell proliferation and increases interferon-gamma and interleukin-10 production; and (iii) induces apoptosis of T lymphocytes through activation of caspase-8 that terminates with fragmentation of DNA. These results are the first to suggest a role for GalXM in C. neoformans virulence by demonstrating that it can target human T cells, and that it may impair the development of an effective specific T cell response. 相似文献
66.
Melanins are enigmatic pigments found in all biological kingdoms that are associated with a variety of functions, including microbial virulence. Despite being ubiquitous in nature, melanin pigments have long resisted atomic-level structural examination because of their insolubility and amorphous organization. Cryptococcus neoformans is a human pathogenic fungus that melanizes only when provided with exogenous substrate, thus offering a unique system for exploring questions related to melanin structure at the molecular level. We have exploited the requirement for exogenous substrate in melanin synthesis as well as the capabilities of high-resolution solid-state nuclear magnetic resonance (NMR) to establish the predominantly aliphatic composition of l-dopa melanin and to introduce (13)C labels that permit the identification of proximal carbons in the developing biopolymer. By swelling solid melanin samples in organic solvents and using two-dimensional heteronuclear NMR in conjunction with magic-angle spinning, we have identified chemical bonding patterns typical of alkane, alkene, alcohol, ketone, ester, and indole functional groups. These findings demonstrate the feasibility of a novel approach to determining the structure of melanin using metabolic labeling and NMR spectroscopy. 相似文献
67.
The late twentieth century witnessed the emergence of numerous infectious diseases that are caused by microorganisms that rarely cause disease in normal, healthy immunocompetent hosts. The emergence of these diseases shows that the existing concepts of pathogenicity and virulence do not take into account the fact that both the microorganism and the host contribute to microbial pathogenesis. To address this impediment to studies of host-microorganism interactions, we propose a new theoretical approach to understanding microbial pathogenesis, known as the 'damage-response' framework. 相似文献
68.
Schwebach JR Chen B Glatman-Freedman A Casadevall A McKinney JD Harb JL McGuire PJ Barkley WE Bloom BR Jacobs WR 《Applied and environmental microbiology》2002,68(9):4646-4649
Aerosolized delivery of virulent or hypervirulent Mycobacterium tuberculosis requires careful consideration of methodology and safety. To maximize safety, we installed a nose-only aerosol apparatus that can reproducibly deliver a low dose (<100 CFU per mouse) of M. tuberculosis in a carefully designed biohazard facility. 相似文献
69.
Cryptococcus neoformans strains exhibit considerable phenotype variability with regards to the capsular polysaccharide, sterol composition of the cell wall, and cell and colony morphology. Phenotypic changes can occur spontaneously during in vitro passage of strains or during chronic infection in vivo and may be associated with differences in virulence. Studies from our laboratory have demonstrated that phenotype variability can be the result of phenotypic switching. Phenotypic switching is defined as a reversible change of an observable colony phenotype that occurs at a frequency above the expected frequency for somatic mutations. This implies that phenotypic switching represents controlled and programmed changes in this pathogenic yeast rather than random mutations. We have shown that a phenotypic switch from a smooth colony phenotype to a mucoid colony phenotype occurs in vitro and in vivo during chronic infection of mice. More importantly we have now demonstrated that the switch is associated with an increase in virulence and a change in the host immune response. Implications of these findings for the pathogenesis of cryptococcosis are discussed. 相似文献
70.
The green unicellular alga Botryococcus braunii shows unusually high concentrations of non-isoprenoid very long chain hydrocarbons. The structure of such hydrocarbons, the relative efficiency of various long chain fatty acids as precursors, the relationship between fatty acid and hydrocarbon concentrations (over the different physiological stages of the alga achieved during batch cultures) and the preferential localization of fatty acids lead to the conclusion that all the major non-isoprenoid hydrocarbons of B. braunii derive from the same direct precursor, oleic acid. Feeding experiments, using doubly labelled oleic acid, show that the whole carbon chain of the latter is incorporated into final hydrocarbons; accordingly such compounds do not originate from a head-to-head condensation mechanism with oleic acid acting as donor. Various features (regarding chiefly the systematic occurrence of a terminal double bond in B. braunii hydrocarbon, their close specific activities after feeding and the large inhibition in their production achieved using dithioerythritol) show that the biosynthesis of B. braunii hydrocarbons probably takes place via an elongation-decarboxylation mechanism related to that operating in some higher plants. 相似文献