Differential activation of a Candida albicans virulence gene family during infection.
The yeast Candida albicans is a harmless commensal in most healthy people, but it causes superficial as well as life-threatening systemic infections in immunocompromised patients. C. albicans can colonize or infect virtually all body sites because of its high adaptability to different host niches, which involves the activation of appropriate sets of genes in response to complex environmental signals. We have used an in vivo expression technology that is based on genetic recombination as a reporter of gene expression to monitor the differential activation of individual members of a gene family encoding secreted aspartic proteinases (Saps), which have been implicated in C. albicans virulence, at various stages of the infection process. Our results demonstrate that SAP expression depends on the type of infection, with different SAP isogenes being activated during systemic disease as compared with mucosal infection. In addition, the activation of individual SAP genes depends on the progress of the infection, some members of the gene family being induced immediately after contact with the host, whereas others are expressed only after dissemination into deep organs. In the latter case, the number of invading organisms determines whether induction of a virulence gene is necessary for successful infection. The in vivo expression technology allows the elucidation of gene expression patterns at different stages of the fungus-host interaction, thereby revealing regulatory adaptation mechanisms that make C. albicans the most successful fungal pathogen of humans and, at the same time, identifying the stage of an infection at which certain virulence genes may play a role.
Staib
P
P
Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.
Kretschmar
M
M
Nichterlein
T
T
Hof
H
H
Morschhäuser
J
J
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002176:Candida albicans / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D002177:Candidiasis / Q000201:enzymology* / Q000382:microbiology; D004790:Enzyme Induction; D004941:Esophagitis / Q000201:enzymology / Q000382:microbiology; D005260:Female; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016469:Fungemia / Q000201:enzymology / Q000382:microbiology; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity; D010538:Peritonitis / Q000201:enzymology / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D011995:Recombination, Genetic; D014774:Virulence / Q000235:genetics
D005656:Fungal Proteins; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D016282:Aspartic Acid Endopeptidases