Affiliation:
1. Institut für Allgemeine Botanik, AMPIII, Universität Hamburg, D-22609 Hamburg
2. Robert Koch-Institut, D-13353 Berlin, Germany
3. Institut für Medizinische Mikrobiologie und Hygiene, Klinikum Mannheim, D-68135 Mannheim
4. Klinik und Poliklinik für Dermatologie und Allergologie, Ludwig-Maximilians-Universität München, D-80337 Munich
5. Institut de Microbiologie, Centre Hospitalier Universitaire Vaudoise, CH-1011 Lausanne, Switzerland
Abstract
ABSTRACT
The ability to change between yeast and hyphal cells (dimorphism) is known to be a virulence property of the human pathogen
Candida albicans
. The pathogenesis of disseminated candidosis involves adhesion and penetration of hyphal cells from a colonized mucosal site to internal organs. Parenchymal organs, such as the liver and pancreas, are invaded by
C. albicans
wild-type hyphal cells between 4 and 24 h after intraperitoneal (i.p.) infection of mice. In contrast, a hypha-deficient mutant lacking the transcription factor Efg1 was not able to invade or damage these organs. To investigate whether this was due to the inability to undergo the dimorphic transition or due to the lack of hypha-associated factors, we investigated the role of secreted aspartic proteinases during tissue invasion and their association with the different morphologies of
C. albicans
. Wild-type cells expressed a distinct pattern of
SAP
genes during i.p. infections. Within the first 72 h after infection,
SAP1
,
SAP2
,
SAP4
,
SAP5
,
SAP6
, and
SAP9
were the most commonly expressed proteinase genes. Sap1 to Sap3 antigens were found on yeast and hyphal cells, while Sap4 to Sap6 antigens were predominantly found on hyphal cells in close contact with host cells, in particular, eosinophilic leukocytes. Mutants lacking
EFG1
had either noticeably reduced or higher expressed levels of
SAP4
to
SAP6
transcripts in vitro depending on the culture conditions. During infection,
efg1
mutants had a strongly reduced ability to produce hyphae, which was associated with reduced levels of
SAP4
to
SAP6
transcripts. Mutants lacking
SAP1
to
SAP3
had invasive properties indistinguishable from those of wild-type cells. In contrast, a triple mutant lacking
SAP4
to
SAP6
showed strongly reduced invasiveness but still produced hyphal cells. When the tissue damage of liver and pancreas caused by single
sap4
,
sap5
, and
sap6
and double
sap4
and -
6
,
sap5
and -
6
, and
sap4
and -
5
double mutants was compared to the damage caused by wild-type cells, all mutants which lacked functional
SAP6
showed significantly reduced tissue damage. These data demonstrate that strains which produce hyphal cells but lack hypha-associated proteinases, particularly that encoded by
SAP6
, are less invasive. In addition, it can be concluded that the reduced virulence of hypha-deficient mutants is not only due to the inability to form hyphae but also due to modified expression of the
SAP
genes normally associated with the hyphal morphology.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
219 articles.
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