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ARTICLE

Engineered Control of Cell Morphology In Vivo Reveals Distinct Roles for Yeast and Filamentous Forms of Candida albicans during Infection

Stephen P. Saville, Anna L. Lazzell, Carlos Monteagudo, Jose L. Lopez-Ribot
Stephen P. Saville
1Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245
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  • For correspondence: saville@uthscsa.edu
Anna L. Lazzell
1Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245
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Carlos Monteagudo
2Departmento de Patología, Facultad de Medicina y Odontología, Universidad de Valencia, 46010 Valencia, Spain
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Jose L. Lopez-Ribot
1Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245
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DOI: 10.1128/EC.2.5.1053-1060.2003
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ABSTRACT

It is widely assumed that the ability of Candida albicans to switch between different morphologies is required for pathogenesis. However, most virulence studies have used mutants that are permanently locked into either the yeast or filamentous forms which are avirulent but unsuitable for discerning the role of morphogenetic conversions at the various stages of the infectious process. We have constructed a strain in which this developmental transition can be externally modulated both in vitro and in vivo. This was achieved by placing one copy of the NRG1 gene (a negative regulator of filamentation) under the control of a tetracycline-regulatable promoter. This modified strain was then tested in an animal model of hematogenously disseminated candidiasis. Mice injected with this strain under conditions permitting hyphal development succumbed to the infection, whereas all of the animals injected under conditions that inhibited this transition survived. Importantly, fungal burdens were almost identical in both sets of animals, indicating that, whereas filament formation appears to be required for the mortality resulting from a deep-seated infection, yeast cells play an important role early in the infectious process by extravasating and disseminating to the target organs. Moreover, these infecting Candida yeast cells still retained their pathogenic potential, as demonstrated by allowing this developmental transition to occur at various time points postinfection. We demonstrate here the importance of morphogenetic conversions in C. albicans pathogenesis. This engineered strain should provide a useful tool in unraveling the individual contributions of the yeast and filamentous forms at various stages of the infectious process.

  • Copyright © 2003 American Society for Microbiology
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Engineered Control of Cell Morphology In Vivo Reveals Distinct Roles for Yeast and Filamentous Forms of Candida albicans during Infection
Stephen P. Saville, Anna L. Lazzell, Carlos Monteagudo, Jose L. Lopez-Ribot
Eukaryotic Cell Oct 2003, 2 (5) 1053-1060; DOI: 10.1128/EC.2.5.1053-1060.2003

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Engineered Control of Cell Morphology In Vivo Reveals Distinct Roles for Yeast and Filamentous Forms of Candida albicans during Infection
Stephen P. Saville, Anna L. Lazzell, Carlos Monteagudo, Jose L. Lopez-Ribot
Eukaryotic Cell Oct 2003, 2 (5) 1053-1060; DOI: 10.1128/EC.2.5.1053-1060.2003
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KEYWORDS

Candida albicans
Candidiasis
Hyphae
Repressor Proteins
Yeasts

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