Spontaneous mutant of<i>Blastomyces dermatitidis</i>attenuated in virulence for mice

Brass, Corstiaan; Volkmann, Carol M.; Philpott, Delbert E.; Klein, Harold P.; Halde, Carlyn; Stevens, David A.

doi:10.1080/00362178285380221

Cited by 41 publications

(27 citation statements)

References 5 publications

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“…The mechanism(s) by which fungi acquire and maintain virulence for mammalian hosts in a life cycle that does not require animal parasitism is unexplained. Virulence for many environmental fungal pathogens is not constitutive, and passage of fungi in the laboratory can lead to virulence attenuation (4,5,14). Since virulence is almost always a complex trait, the pathogenicity of certain saprophytic fungi for mammals poses the question of how virulence is selected for and maintained in the environment (7,35).…”

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Interaction ofBlastomyces dermatitidis,Sporothrix schenckii, andHistoplasma capsulatumwithAcanthamoeba castellanii

et al. 2004

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Several dimorphic fungi are important human pathogens, but the origin and maintenance of virulence in these organisms is enigmatic, since an interaction with a mammalian host is not a requisite for fungal survival. Recently, Cryptococcus neoformans was shown to interact with macrophages, slime molds, and amoebae in a similar manner, suggesting that fungal pathogenic strategies may arise from environmental interactions with phagocytic microorganisms. In this study, we examined the interactions of three dimorphic fungi with the soil amoeba Acanthameobae castellanii. Yeast forms of Blastomyces dermatitidis, Sporothrix schenckii, and Histoplasma capsulatum were each ingested by amoebae and macrophages, and phagocytosis of yeast cells resulted in amoeba death and fungal growth. H. capsulatum conidia were also cytotoxic to amoebae. For each fungal species, exposure of yeast cells to amoebae resulted in an increase in hyphal cells. Exposure of an avirulent laboratory strain of H. capsulatum to A. castellanii selected for, or induced, a phenotype of H. capsulatum that caused a persistent murine lung infection. These results are consistent with the view that soil amoebae may contribute to the selection and maintenance of certain traits in pathogenic dimorphic fungi that confer on these microbes the capacity for virulence in mammals.

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Interaction ofBlastomyces dermatitidis,Sporothrix schenckii, andHistoplasma capsulatumwithAcanthamoeba castellanii

et al. 2004

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“…The discrepancy between their findings and ours might be explained by recent findings about spontaneous variation of ATCC strain 26199. Mutants of 26199 have arisen spontaneously by serial passage in vitro: ATCC 60915 is an attenuated mutant (22), and ATCC 60916 is avirulent (23). Phenotypic alterations recently documented in these mutants include partial or complete loss of surface α-(1,3)-glucan (24) and changes in the amount of surface and secreted WI-1 (25).…”

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Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance

Filutowicz²,

2000

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“…American Type Culture Collection (Manassas, Va.) strains 26199 and 60916 were used in this study. Strain 26199 was originally isolated from a human patient, and strain 60916 was derived from strain 26199 through serial passages (3). Yeast cells of strain 26199 express both glucan and BAD1, whereas yeast cells of strain 60916 express undetectable amounts of ␣-glucan (7), much less ␤-glucan (M. X. Zhang and B. S. Klein, unpublished data), and 5 to 10 times more BAD1 than do those of the parental strain (11).…”

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Role of Glucan and Surface Protein BAD1 in Complement Activation byBlastomyces dermatitidisYeast

et al. 2001

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Our previous studies showed that Blastomyces dermatitidis yeast activates the human complement system, leading to deposition of opsonic complement fragments onto the yeast surface. This report examines the influence of altered surface expression of glucan or BAD1 protein (formerly WI-1) on the yeast's ability to activate and bind C3. Compared to the wild type, a glucan-deficient mutant yeast delayed initiation of C3 deposition and reduced C3-binding capacity by 50%. Linkage of baker's-yeast ␤-glucan to the glucan-deficient yeast restored initial C3 deposition kinetics to the wild-type level and partially restored C3-binding capacity, suggesting that ␤-glucan is an initiator of complement activation and a C3 acceptor. The role of BAD1 in B. dermatitidis yeast-complement interaction was also assessed. BAD1 knockout yeast initiated faster C3 deposition and increased C3-binding capacity compared to the wild-type yeast or a BAD1-reconstituted yeast, suggesting either a lack of an intrinsic ability in BAD1 or an inhibitory role of BAD1 in complement activation and binding. However, both complement activation and the capacity for C3 binding by the wild-type yeast were enhanced in normal human serum supplemented with an anti-BAD1 monoclonal antibody (MAb) or in immune sera from blastomycosis patients. Microscopic analysis revealed that more initial C3-binding sites were formed on yeast in the presence of both naturally occurring complement initiators and exogenous anti-BAD1 MAb, suggesting that anti-BAD1 antibody enhanced the ability of B. dermatitidis yeast to interact with the host complement system. Thus, glucan and BAD1 have distinctly different regulatory effects on complement activation by B. dermatitidis.Blastomyces dermatitidis is the etiological agent of blastomycosis, which is one of the principal endemic systemic mycoses of humans and other mammals (22). Host defense mechanisms against B. dermatitidis infection include the complement system. Complement promotes attachment of human phagocytes to B. dermatitidis and is required for neutrophil-mediated killing of B. dermatitidis yeast (5). Our previous studies showed that B. dermatitidis yeast cells activate the human complement system via both the classical and alternative pathways, leading to deposition of C3b and iC3b complement fragments on the yeast surface (26). Furthermore, we found that naturally occurring anti-␤-glucan antibodies promote activation of the classical complement pathway by the yeast (26). How yeast cell surface structures modulate the yeast's ability to interact with the human complement system remains unknown.The cell surface of B. dermatitidis yeast is associated with a dynamic array of proteins and carbohydrates. Prominent among them are glucan and surface protein BAD1, formerly termed WI-1 (21), both of which have been implicated as virulence factors (2, 10). About 95% of the glucan components are ␣-glucan, and the remainder are ␤-glucan (8). BAD1 is a 120-kDa immunodominant antigen; it is also an adhesin that binds the yeast to CD14 a...

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Spontaneous mutant ofBlastomyces dermatitidisattenuated in virulence for mice

Cited by 41 publications

References 5 publications

Interaction ofBlastomyces dermatitidis,Sporothrix schenckii, andHistoplasma capsulatumwithAcanthamoeba castellanii

Interaction ofBlastomyces dermatitidis,Sporothrix schenckii, andHistoplasma capsulatumwithAcanthamoeba castellanii

Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance

Role of Glucan and Surface Protein BAD1 in Complement Activation byBlastomyces dermatitidisYeast

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