-
International Journal of Medical... Oct 2002Histoplasma capsulatum is a dimorphic ascomycete which is capable of producing a broad spectrum of disease ranging from mild asymptomatic, pulmonary illness to severe,... (Review)
Review
Histoplasma capsulatum is a dimorphic ascomycete which is capable of producing a broad spectrum of disease ranging from mild asymptomatic, pulmonary illness to severe, life-threatening systemic mycosis. Regulatory mechanisms that use temperature and other environmental cues are paramount to the successful adaptation of the organism as an effective intracellular pathogenic yeast. Although the biochemistry and phenomenology of reversible morphogenesis have been well examined in Histoplasma, the identification and functional characterization of genes and their products that are required for early establishment or maintenance of the parasitic yeast phase in intracellular host compartments have only recently been fruitful. Advances in the molecular biology of Histoplasma, including approaches to introduce telomeric plasmids, reporter fusion constructs, and gene disruption cassettes into the fungus are poised to solidify the pre-eminence of this fungus as a model system which can be applied to other dimorphic fungal pathogens that exhibit similar cellular and immunological complexities. This review centers on recent developments in the molecular cell biology and molecular genetics of Histoplasma capsulatum that provide important new avenues for examining the mold-to-yeast phase transition beyond the historical, binary view of dimorphism and the implications that these successful approaches may have on seminal issues in fungal pathogenesis.
Topics: Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Humans; Mutation; Phagosomes; Phenotype; Temperature; Virulence
PubMed: 12452281
DOI: 10.1078/1438-4221-00218 -
Clinical Microbiology Reviews Oct 1991This review summarizes the biology of Histoplasma capsulatum in relation to a wide variety of corresponding pathologies in histoplasmosis. Features of these disease... (Review)
Review
This review summarizes the biology of Histoplasma capsulatum in relation to a wide variety of corresponding pathologies in histoplasmosis. Features of these disease syndromes can be explained in part by natural variations within the fungal population and adaptations made by individual organisms to specific environments. H. capsulatum grows as mycelia and conidia in the soil; once inhaled, the organism undergoes a dramatic morphological and physiological conversion to a yeast form. The yeasts proliferate within the phagolysosomes of macrophages, using a variety of specific strategies for intracellular survival. Even avirulent strains or variants are able to avoid being killed by macrophages and instead establish inapparent or persistent infections. The ingested avirulent organisms assume enlarged shapes similar in appearance to those seen in histological sections of tissues from patients with histoplasmosis. Respiratory tract epithelial cells also appear to play a role in persistence: within them yeasts undergo phenotypic switching akin to the phase variation observed in other pathogens. This particular change involves the loss or modification of cell wall alpha-(1,3)-glucan, which is also correlated with the spontaneous appearance of avirulent variants. The repertoire of adaptive responses and natural variations within this species probably evolved from the need to adjust to a wide range of dynamic environments. In combination with the immune status of the host, these characteristics of H. capsulatum appear to influence the epidemiology, extent, and persistence of histoplasmosis.
Topics: Animals; Histoplasma; Histoplasmosis; Host-Parasite Interactions; Humans
PubMed: 1747859
DOI: 10.1128/CMR.4.4.411 -
Verhandelingen - Koninklijke Academie... 1995Early in the developmental period of microbiology, Pasteur first observed the phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew as a... (Review)
Review
Early in the developmental period of microbiology, Pasteur first observed the phenomenon of dimorphism in fungi when he noticed that the bread mold Mucor grew as a filamentous mold aerobically on the surface of broth cultures but at the bottom of the flask where the environment was anaerobic it reproduced as budding yeast cells. Several infectious fungal pathogens of humans, namely Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Sporothrix schenkii, and Coccidioides immitis change from a multicellular filamentous form to an unicellular morphology when they invade tissues. The ability of pathogenic fungi to assume a different shape is referred to as dimorphism. This phenomenon has intrigued clinicians, and medical mycologists since its discovery at the turn of the century. The ability of pathogens to initiate infection, invade host tissues and survive in mammalian hosts is critically linked to the induction of specific gene products. In dimorphic fungi, developmentally regulated gene expression is particularly important, since they may exist in phylogenetically distinct hosts with different body temperatures. Using Histoplasma capsulatum as a model to study parasite-host interactions at the biochemical and molecular level, my laboratory has attempted to relate the clinical spectrum of disease to natural variations in the characteristics of this organism and to adaptations it must make as a saprobe and a parasite. Histoplasma capsulatum is the etiologic agent of histoplasmosis, a respiratory infection that is world-wide in distribution. As a saprobe in soil it is mycelial, but it becomes a budding yeast as a parasite in susceptible hosts. These morphological phases can be reversibly reproduced in vitro by shifting the temperature from 25 degrees C, at which it is mycelial, to 37 degrees C, when it becomes a budding yeast. The process of mycelial-to-yeast conversion is of particular interest since it is triggered by an increase in temperature and conversion to virulence. Viable mycelial fragments and conidia become airborne and enter the pulmonary tract by inhalation after which the fungus rapidly disseminates to other organs. Progressive disseminated histoplasmosis along with candidiasis, cryptococcosis, and invasive aspergillosis are opportunistic fungal infections in patients who are immunosuppressed or otherwise debilitated. Importantly, they are diagnostic hallmarks of acquired immunodeficiency disease syndrome (AIDS). The clinical features of these infections and the genetic characteristics of the etiologic agents present unique parasite-host interactions that make them valuable research models to study. In the infected host, Histoplasma capsulatum encounters various environmental stresses to which it adapts by regulating the expression of specific genes.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Adaptation, Physiological; Base Sequence; Fatty Acid Desaturases; Heat-Shock Proteins; Histoplasma; Histoplasmosis; Host-Parasite Interactions; Humans; Molecular Sequence Data; Saccharomyces cerevisiae; Stearoyl-CoA Desaturase
PubMed: 7571855
DOI: No ID Found -
Mycoses Jan 2016Histoplasmosis is a systemic fungal disease that occurs worldwide, causing symptomatic infection mostly in immunocompromised hosts. Etiological agent is the dimorphic...
Histoplasmosis is a systemic fungal disease that occurs worldwide, causing symptomatic infection mostly in immunocompromised hosts. Etiological agent is the dimorphic fungus, Histoplasma capsulatum, which occurs in soil contaminated with bird or bat droppings. Major limitation in recognition of H. capsulatum infections is the low awareness, since other diseases may have similar symptomatology. The molecular methods have gained importance because of unambiguous diagnostic ability and efficiency. The aim of this study was to develop and evaluate a padlock probe in view of rolling circle amplification (RCA) detection method which targets ITS (Internal Transcribed Spacer) rDNA of H. capsulatum enabling rapid and specific detection of the fungus in clinical samples. Two padlock probes were designed and one of these (HcPL2) allowed specific amplification of H. capsulatum DNA while no cross-reactivity was observed with fungi used as negative controls. This method proved to be effective for H. capsulatum specific identification and demonstrated to be faster than the traditional method of microbiological identification.
Topics: Animals; DNA Probes; DNA, Fungal; DNA, Ribosomal Spacer; Histoplasma; Histoplasmosis; Humans; Nucleic Acid Amplification Techniques; Phylogeny; Sensitivity and Specificity
PubMed: 26578301
DOI: 10.1111/myc.12426 -
Fungal Genetics and Biology : FG & B Mar 2002Histoplasma capsulatum is a thermally dimorphic ascomycete that is a significant cause of respiratory and systemic disease in mammals including humans, especially... (Review)
Review
Histoplasma capsulatum is a thermally dimorphic ascomycete that is a significant cause of respiratory and systemic disease in mammals including humans, especially immunocompromised individuals such as AIDS patients. As an environmental mold found in the soil, it is a successful member of a competitive polymicrobial ecosystem. Its host-adapted yeast form is a facultative intracellular pathogen of mammalian macrophages. H. capsulatum faces a variety of environmental changes during the course of infection and must survive under harsh conditions or modulate its microenvironment to achieve success as a pathogen. Histoplasmosis may be considered the fungal homolog of the bacterial infection tuberculosis, since both H. capsulatum and Mycobacterium tuberculosis exploit the macrophage as a host cell and can cause acute or persistent pulmonary and disseminated infection and reactivation disease. The identification and functional analysis of biologically or pathogenically important H. capsulatum genes have been greatly facilitated by the development of molecular genetic experimental capabilities in this organism. This review focuses on responsiveness of this fungus to its environment, including differential expression of genes and adaptive phenotypic traits.
Topics: Animals; Cells, Cultured; Histoplasma; Histoplasmosis; Humans; Immunocompromised Host; Macrophages; Phenotype; Sex Characteristics; Soil Microbiology; Transferrin; Virulence
PubMed: 11848673
DOI: 10.1006/fgbi.2001.1311 -
Current Opinion in Microbiology Aug 2003Histoplasma capsulatum is a successful intracellular pathogen of mammalian macrophages. As such, this fungus must survive and/or subvert hostile environmental onslaughts... (Review)
Review
Histoplasma capsulatum is a successful intracellular pathogen of mammalian macrophages. As such, this fungus must survive and/or subvert hostile environmental onslaughts in a professionally antimicrobial host cell. H. capsulatum uses different host receptors for binding to macrophages (beta 2 integrins) than it uses for binding to dendritic cells (the fibronectin receptor); the fungus experiences different degrees of success in survival in these two cells. Surface expression of HSP60 as the specific adhesin for macrophage beta 2 integrins represents a novel mechanism for binding. Long considered a resident of the phagolysosome, H. capsulatum may also reside in a modified phagosome without experiencing phagolysosomal fusion. H. capsulatum must compete with the host to acquire the essential nutrient iron, and has several potential mechanisms for accomplishing this necessary feat. Finally, H. capsulatum displays morphotype-specific expression of several genes, and a calcium-binding protein expressed only by the pathogenic yeast phase has been demonstrated as essential for full virulence. An organism's environment is of great importance to its success or failure, and H. capsulatum is good at finding or making the right environment in the host.
Topics: Animals; Histoplasma; Histoplasmosis; Humans; Iron; Virulence
PubMed: 12941399
DOI: 10.1016/s1369-5274(03)00080-8 -
Archives of Medical Research 1993In the dimorphic fungus Histoplasma capsulatum the expression of heat shock genes is modulated by addition of fatty acids. Addition at 25 degrees C of saturated fatty... (Review)
Review
In the dimorphic fungus Histoplasma capsulatum the expression of heat shock genes is modulated by addition of fatty acids. Addition at 25 degrees C of saturated fatty acid (palmitic acid) to mycelia of H. capsulatum induced a significant increase in heat shock mRNAs transcription when cells were heat shocked. Conversely, treatments with unsaturated fatty acid (oleic acid) drastically reduced the level of heat shock gene transcription at 37 degrees C, and no detectable levels were measurable with 2 mM. Addition of saturated fatty acid induced a thermotolerant state and mitochondria retained ATPase activity coupled to electron transport under severe heat shock conditions and shortened the time required for mycelium-to-yeast phase transition. Conversely, addition of unsaturated fatty acids uncoupled mitochondrial electron transport and prolonged considerably the time required for phase transition at the same temperatures. A virulent strain, if treated with unsaturated fatty acid under condition in which no heat shock was detectable, lost its virulence probably as a consequence of decreased ability to adapt to the new living condition present in the host.
Topics: Cell Membrane; Fungal Proteins; Gene Expression Regulation, Fungal; Heat-Shock Proteins; Histoplasma; Membrane Fluidity; Oleic Acid; Oleic Acids; Palmitic Acid; Palmitic Acids; Temperature; Transcription, Genetic; Virulence
PubMed: 8298273
DOI: No ID Found -
Mykosen Jul 1968
Review
Topics: Animals; Antigens; Fluorescent Antibody Technique; Histoplasma; Horses; Lymphangitis; Species Specificity
PubMed: 4920341
DOI: 10.1111/j.1439-0507.1968.tb03370.x -
The American Review of Respiratory... Dec 1965
Review
Topics: Antigens; Cell Membrane; Histoplasma; In Vitro Techniques
PubMed: 5320843
DOI: 10.1164/arrd.1965.92.6P2.119 -
Current Opinion in Microbiology Aug 2000Knowledge of the host response to the intracellular pathogenic fungus Histoplasma capsulatum has increased dramatically. Information has accumulated regarding the... (Review)
Review
Knowledge of the host response to the intracellular pathogenic fungus Histoplasma capsulatum has increased dramatically. Information has accumulated regarding the cellular and molecular determinants that lead to resolution of both primary and secondary infection. The significance of cytokines and other endogenous soluble mediators to the protective immune response have been analyzed. Moreover, work concerning the relative importance of T cell subsets to protective immunity has been initiated.
Topics: Animals; Cytokines; Histoplasma; Histoplasmosis; Humans; Mice; T-Lymphocytes
PubMed: 10972494
DOI: 10.1016/s1369-5274(00)00104-1