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Infection and Immunity, June 2009, p. 2343-2355, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01458-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role for Endosomal and Vacuolar GTPases in Candida albicans Pathogenesis{triangledown}

Douglas A. Johnston,1 Karen E. Eberle,2 Joy E. Sturtevant,1 and Glen E. Palmer1,2*

Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center School of Dentistry, 1100 Florida Avenue, Box F8-130, New Orleans, Louisiana 70119,1 Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, 1100 Florida Avenue, New Orleans, Louisiana 701122

Received 28 November 2008/ Returned for modification 24 December 2008/ Accepted 26 March 2009

The vacuole has crucial roles in stress resistance and adaptation of the fungal cell. Furthermore, in Candida albicans it has been observed to undergo dramatic expansion during the initiation of hyphal growth, to produce highly "vacuolated" subapical compartments. We hypothesized that these functions may be crucial for survival within the host and tissue-invasive hyphal growth. We also considered the role of the late endosome or prevacuole compartment (PVC), a distinct organelle involved in vacuolar and endocytic trafficking. We identified two Rab GTPases, encoded by VPS21 and YPT72, required for trafficking through the PVC and vacuole biogenesis, respectively. Deletion of VPS21 or YPT72 led to mild sensitivities to some cellular stresses. However, deletion of both genes resulted in a synthetic phenotype with severe sensitivity to cellular stress and impaired growth. Both the vps21{Delta} and ypt72{Delta} mutants had defects in filamentous growth, while the double mutant was completely deficient in polarized growth. The defects in hyphal growth were not suppressed by an "active" RIM101 allele or loss of the hyphal repressor encoded by TUP1. In addition, both single mutants had significant attenuation in a mouse model of hematogenously disseminated candidiasis, while the double mutant was rapidly cleared. Histological examination confirmed that the vps21{Delta} and ypt72{Delta} mutants are deficient in hyphal growth in vivo. We suggest that the PVC and vacuole are required on two levels during C. albicans infection: (i) stress resistance functions required for survival within tissue and (ii) a role in filamentous growth which may aid host tissue invasion.

* Corresponding author. Mailing address: Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center School of Dentistry, 1100 Florida Avenue, Box F8-130, New Orleans, LA 70119. Phone: (504) 941-8320. Fax: (504) 941-8319. E-mail: gpalme{at}lsuhsc.edu

{triangledown} Published ahead of print on 13 April 2009.

Editor: A. Casadevall

Infection and Immunity, June 2009, p. 2343-2355, Vol. 77, No. 6
0019-9567/09/$08.00+0     doi:10.1128/IAI.01458-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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