Dimorphism in Histoplasma capsulatum: a model for the study of cell differentiation in pathogenic fungi.

Maresca, Bruno; Kobayashi, George S.

doi:10.1128/mmbr.53.2.186-209.1989

Cited by 108 publications

(48 citation statements)

References 103 publications

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“…Like all of these closely related fungi, H. capsulatum resides in the soil as a saprophytic mould (mycelia). When aerosolized hyphal fragments and conidia are inhaled into the lungs of a mammalian host, they undergo a morphogenetic transition into unicellular haploid yeasts that are facultative intracellular parasites of macrophages (Maresca and Kobayashi, 1989). Although the course of infection is usually self-limiting in immunocompetent hosts, it may produce a progressive, disseminated infection in individuals with impaired cell-mediated immunity as well as in hosts lacking any demonstrable immune defect (Goodwin et al, 1980;Graybill, 1988).…”

Section: Introductionmentioning

confidence: 99%

An α‐(1,4)‐amylase is essential for α‐(1,3)‐glucan production and virulence in Histoplasma capsulatum

Marion

Rappleye

Engle

et al. 2006

Molecular Microbiology

110

136

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SummaryHistoplasma capsulatum is a dimorphic fungus that causes respiratory and systemic disease and is capable of surviving and replicating within macrophages. The virulence of Histoplasma has been linked to cell wall a-(1,3)-glucan; however, the role of this polysaccharide during infection, its organization within the cell wall, and its synthesis and regulation remain poorly understood. To identify genes involved in the biosynthesis of a-(1,3)-glucan, we employed a forward genetics strategy to isolate physically marked mutants with reduced a-(1,3)-glucan. Insertional mutants were generated in a virulent strain of H. capsulatum by optimization of Agrobacterium tumefaciens-mediated transformation. Approximately 90% of these mutants possessed single insertions with no chromosomal rearrangements or deletions in the host genome. To confirm the role and specificity of identified candidate genes, we phenocopied the disrupted locus by either RNA interference or targeted gene deletion. Our findings indicate a-(1,3)-glucan production requires the function of the AMY1 gene product, a novel protein with homology to the a-amylase family of glycosyl hydrolases, and UGP1, a UTP-glucose-1-phosphate uridylyltransferase which synthesizes UDP-glucose monomers. Loss of AMY1 function attenuated the ability of Histoplasma to kill macrophages and to colonize murine lungs.

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Section: Introductionmentioning

confidence: 99%

An α‐(1,4)‐amylase is essential for α‐(1,3)‐glucan production and virulence in Histoplasma capsulatum

Marion

Rappleye

Engle

et al. 2006

Molecular Microbiology

110

136

View full text Add to dashboard Cite

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“…When mycelia or conidia are inhaled by the mammalian host, the organism converts to unioellular yeasts that are facultative intracellular parasites of macrophages (Eissenberg and Goldman, 1991). This reversible mould/yeast phase transition may be induced in the laboratory by growing the organism at room temperature or at 37°C (Maresca and Kobayashi, 1989). Based on skin-test antigenic reactivity, infection with the organism is extremely common in endemic areas, such as the American Midwest; however, severe disease is rare.…”

Section: Introductionmentioning

confidence: 99%

In vivo generation of linear plasmids with addition of telomeric sequences by Histoplasma capsulatum

Woods

Goldman

1992

Molecular Microbiology

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Histoplasma capsulatum is a dimorphic pathogenic fungus that is a major cause of respiratory and systemic mycosis. We previously developed a transformation system for Histoplasma and demonstrated chromosomal integration of transforming plasmid sequences. In this study, we describe another Histoplasma mechanism for maintaining transforming DNA i.e. the generation of modified, multicopy linear plasmids carrying DNA from the transforming Escherichia coli plasmid. Under selective conditions, these linear plasmids were stable and capable of retransforming Histoplasma without further modification. In vivo modification of the transforming DNA included duplication of plasmid sequence and telomeric addition at the termini of linear DNA. Apparently Histoplasma telomerase, like that of other organisms such as humans and Tetrahymena, is able to act on non-telomeric substrates. The terminus of a Histoplasma linear plasmid was cloned and shown to contain multiple repeats of GGGTTA, the telomeric repeat unit also found in vertebrates, trypanosomes, and slime moulds.

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“…Furthermore, the infectious stage for some pathogens, like P. carinii, or Cryptococcus neoformans, remains to be identified [22]. Virulence factors that are under investigation are secreted protease [24], phospholipase [25], the ability to change the growth form (dimorphism) [26,27] and capsule formation [28]. In addition, adherence to cell surfaces and the potential to penetrate into cells could be important determinants for the course of a fungal infection [29].…”

Section: Mechanisms Of Pathogenesismentioning

confidence: 99%

Molecular genetics of pathogenic fungi: some recent developments and perspectives

Ernst

1990

Mycoses

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The diagnosis and the treatment of fungal diseases remains problematic in many cases. Difficulties in diagnosis are due (1) to the ubiquitous presence of fungal pathogens that may lead to false positive test results and (2) to difficulties in the evaluation of the aetiological significance of these pathogens. The relatively small number of effective antifungal agents reflects to a large extent on the fact that many aspects of fungal physiology and virulence are not well understood. The methods of molecular genetics provide effective tools for the diagnosis of mycoses and may also contribute to the identification of new targets for antifungals by genetic analyses of fungal virulence. During the last 3 years molecular genetic methods have been developed for the asexual pathogen Candida albicans that may be used for strain identification. This success indicates a general use of molecular genetics for the analysis of fungal pathogenesis.

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Dimorphism in Histoplasma capsulatum: a model for the study of cell differentiation in pathogenic fungi.

Cited by 108 publications

References 103 publications

An α‐(1,4)‐amylase is essential for α‐(1,3)‐glucan production and virulence in Histoplasma capsulatum

An α‐(1,4)‐amylase is essential for α‐(1,3)‐glucan production and virulence in Histoplasma capsulatum

In vivo generation of linear plasmids with addition of telomeric sequences by Histoplasma capsulatum

Molecular genetics of pathogenic fungi: some recent developments and perspectives

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