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Eukaryotic Cell, October 2003, p. 1053-1060, Vol. 2, No. 5
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.5.1053-1060.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Stephen P. Saville,1* Anna L. Lazzell,1 Carlos Monteagudo,2 and Jose L. Lopez-Ribot1

Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245,1 Departmento de Patología, Facultad de Medicina y Odontología, Universidad de Valencia, 46010 Valencia, Spain2

Received 24 July 2003/ Accepted 29 July 2003

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.

* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, STCBM, 15355 Lambda Dr., San Antonio, TX 78245. Phone: (210) 562-5018. Fax: (210) 562-5016. E-mail: saville{at}uthscsa.edu.

Eukaryotic Cell, October 2003, p. 1053-1060, Vol. 2, No. 5
1535-9778/03/$08.00+0     DOI: 10.1128/EC.2.5.1053-1060.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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