Electron-microscopic observations of the<i>Coccidioides immitis</i>parasitic cycle<i>in vivo</i>

Sun, Steven; Cole, Garry T.; Drutz, David J.; Harrison, Jeffrey L.

doi:10.1080/02681218680000281

Cited by 37 publications

(21 citation statements)

References 13 publications

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“…C. posadasii strain C735 typically completes its first generation of the parasitic cycle in vitro within 5 to 6 days, and the sequence of morphogenetic events appears to be identical to that observed in vivo (35). In addition, first-generation parasitic cells of strain C735 grown in vitro have been shown to be near-synchronous in their development (18).…”

Section: Resultsmentioning

confidence: 94%

Urease Produced by Coccidioides posadasii Contributes to the Virulence of This Respiratory Pathogen

et al. 2006

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Urease activity during in vitro growth in the saprobic and parasitic phases of Coccidioides spp. is partly responsible for production of intracellular ammonia released into the culture media and contributes to alkalinity of the external microenvironment. Although the amino acid sequence of the urease of Coccidioides posadasii lacks a predicted signal peptide, the protein is transported from the cytosol into vesicles and the central vacuole of parasitic cells (spherules). Enzymatically active urease is released from the contents of mature spherules during the parasitic cycle endosporulation stage. The endospores, together with the urease and additional material which escape from the ruptured parasitic cells, elicit an intense host inflammatory response. Ammonia production by the spherules of C. posadasii is markedly increased by the availability of exogenous urea found in relatively high concentrations at sites of coccidioidal infection in the lungs of mice. Direct measurement of the pH at these infection sites revealed an alkaline microenvironment. Disruption of the urease gene of C. posadasii resulted in a marked reduction in the amount of ammonia secreted in vitro by the fungal cells. BALB/c mice challenged intranasally with the mutant strain showed increased survival, a wellorganized granulomatous response to infection, and better clearance of the pathogen than animals challenged with either the parental or the reconstituted (revertant) strain. We conclude that ammonia and enzymatically active urease released from spherules during the parasitic cycle of C. posadasii contribute to host tissue damage, which exacerbates the severity of coccidioidal infection and enhances the virulence of this human respiratory pathogen.

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Section: Resultsmentioning

confidence: 94%

Urease Produced by Coccidioides posadasii Contributes to the Virulence of This Respiratory Pathogen

et al. 2006

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“…Infected lungs from C57BL/6 mice challenged intranasally with a lethal inoculum of C. posadasii arthroconidia of the parental or ⌬mep1 mutant strain, as reported elsewhere (13), were excised from animals sacrificed at 15 days postchallenge. The lung tissue was chemically fixed, embedded in plastic resin or paraffin, sectioned, and stained with FITCconjugated anti-SOWgp or hematoxylin-eosin in preparation for immunofluorescence or conventional light microscopy as reported elsewhere (8,47).…”

Section: Methodsmentioning

confidence: 99%

A Metalloproteinase of Coccidioides posadasii Contributes to Evasion of Host Detection

et al. 2005

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Coccidioides posadasii is a fungal respiratory pathogen of humans that can cause disease in immunocompetent individuals. Coccidioidomycosis ranges from a mild to a severe infection. It is frequently characterized either as a persistent disease that requires months to resolve or as an essentially asymptomatic infection that can reactivate several years after the original insult. In this report we describe a mechanism by which the pathogen evades host detection during the pivotal reproductive (endosporulation) phase of the parasitic cycle. A metalloproteinase (Mep1) secreted during endospore differentiation digests an immunodominant cell surface antigen (SOWgp) and prevents host recognition of endospores during the phase of development when these fungal cells are most vulnerable to phagocytic cell defenses. C57BL/6 mice were immunized with recombinant SOWgp and then challenged with a mutant strain of C. posadasii in which the MEP1 gene was disrupted. The animals showed a significant increase in percent survival compared to SOWgp-immune mice challenged with the parental strain. To explain these results, we proposed that retention of SOWgp on the surfaces of endospores of the mutant strain in the presence of high titers of antibody to the immunodominant antigen contributes to opsonization, increased phagocytosis, and killing of the fungal cells. In vitro studies of the interaction between a murine alveolar macrophage cell line and parasitic cells coated with SOWgp showed that the addition of anti-SOWgp antibody could enhance phagocytosis and killing of Coccidioides. We suggest that Mep1 plays a pivotal role as a pathogenicity determinant during coccidioidal infections and contributes to the ability of the pathogen to persist within the mammalian host.

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“…These same investigators tested the ability of U. reesii to infect mice. Five Balblc mice (23 g, male) were each inoculated intranasally with a suspension of 1.2 x lo4 arthroconidia of U. reesii in phosphate-buffered saline (pH 7.4) by a method previously reported (Sun et al 1986). No animal deaths were recorded at 4 weeks postinoculation, in contrast to 100% mortality after 10-15 days when mice were inoculated with an equal number of C. immitis arthroconidia.…”

Section: Conidioigenesismentioning

confidence: 99%

Possible roles of wall hydrolases in the morphogenesis ofCoccidioides immitis

Cole¹,

Pishko²,

Seshan³

1995

Can. J. Bot.

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We have used the human respiratory pathogen, Coccidioides immitis, as an experimental model to explore possible interrelationships of wall-associated hydrolases, cell growth, and reproduction. Preliminary evidence has been presented that suggests that certain wall hydrolases (glucanase, chitinase) may play key roles in cell development in this systemic pathogen. Initial differentiation of the parasitic cells from cylindrical arthroconidia involves a period of isotropic growth and results in formation of a multinucleate spherule (approximately 60 pm diameter). An endo-1,3-P-glucanase that may participate in this diametric growth phase has been isolated. Two distinct chitinase genes (ctsl, cts2) have been isolated from C. immitis and shown to be members of different classes of this wall hydrolase. The class I chitinase (CTS2) demonstrates homology to a reported endochitinase of Saccharomyces cerevisiae that has been shown to be essential for yeast daughter cell release. CTS2 may play a pivotal role in isotropic growth, as well as differentiation and release of endospores from maternal spherules. In the absence of specific gene disruption and transformation experiments, these data are still circumstantial evidence for the functions of wall hydrolases in C. immitis development. However, we suggest our results provide further support for the concept that wall hydrolases represent rational molecular targets for future development of novel antifungal agents.R6sum6 : Les auteurs ont utilisC le champignon pathogbne humain Coccidioides imrnitis comme modble expCrimenta1 pour explorer les relations possibles des hydrolases assocites aux parois, avec la croissance cellulaire et la reproduction. Les auteurs prtsentent des ClCments de preuve qui suggbrent que certaines hydrolases pariCtales (glucanase, chitinase) peuvent jouer des r6les clCs dans le developpement cellulaire de ce champignon systCmique. Les premibres diffkrenciations des cellules parasites a partir des arthroconidies cylindriques implique une pCriode de croissance isotropique et conduit a la formation d'une sphCrule multinuclCe (environ 60 pm diambtre). 11s ont isole une endo-1,3-P-glucanase qui peut participer a cette phase de croissance isodiametrique. Deux gbnes de chitinase distincts (ctsl, cts2) ont Ct C isolts du C. immitis et on dCmontre qu'ils sont membres de diffkrentes classes de cette hydrolase pariCtale. La chitinase de classe I (CTS2) montre une homologie avec une endochitinase rapportCe chez le Saccharomyces cerevisiae, dont I'essentialitC pour le reldchement de la cellule fille de la levure a Ct C dCmontrCe. Le CST2 peut jouer un r61e central dans la croissance isotropique aussi bien que dans la diffkrenciation et le reldchement des endospores 1 partir des sphCrules maternelles. En absence de perturbations spCcifiques ou d7expCriences de transformation, ces donnCes ne constituent encore que des preuves circonstantielles pour les fonctions des hydrolases dans le developement du C. immitis. Cependant, les auteurs suggbrent que leurs rksultats suppo...

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Electron-microscopic observations of theCoccidioides immitisparasitic cyclein vivo

Cited by 37 publications

References 13 publications

Urease Produced by Coccidioides posadasii Contributes to the Virulence of This Respiratory Pathogen

Urease Produced by Coccidioides posadasii Contributes to the Virulence of This Respiratory Pathogen

A Metalloproteinase of Coccidioides posadasii Contributes to Evasion of Host Detection

Possible roles of wall hydrolases in the morphogenesis ofCoccidioides immitis

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