The role of secreted aspartyl proteinases in Candida tropicalis invasion and damage of oral mucosa

Candida virulence attributes include the ability to colonize and invade host tissues, and the secretion of hydrolytic enzymes. Although Candida albicans is regarded as the principal fungi causing infections in humans, other species, particularly Candida tropicalis, are increasingly being recognized as human pathogens. Relatively little is known, however, about the virulence attributes associated with C. tropicalis. The present study aimed to investigate epithelial infection by C. tropicalis using a reconstituted human oral epithelium (RHOE) together with confocal laser scanning microscopy and real-time PCR. A comparison of clinical strains was made in terms of tissue colonization, invasion and C. tropicalis secreted aspartyl proteinase (SAPT) gene expression. All C. tropicalis strains were able to colonize RHOE in a strain-dependent manner. After 12 h of infection, C. tropicalis was found to be highly invasive, with extensive tissue damage occurring after 24 h. Real-time PCR of C. tropicalis SAPT1-4 genes showed that expression was strain-dependent, with SAPT2-4 transcripts being frequently detected and SAPT1 rarely detected. Tissue invasion and damage was not inhibited by the presence of pepstatin A. Accordingly, and given that an increase in infection time was not accompanied with an increase in SAPT gene expression, it can be suggested that the proteinases are not involved in invasion and damage of RHOE by C. tropicalis. In summary, C. tropicalis can be considered as highly invasive with the ability to induce significant tissue damage. These features, however, do not appear to be related to specific SAPT gene expression.We would like to thank Mrs Kath Allsopp for processing and sectioning the tissue samples. This work was supported by grant SFRH/BD/28341/2006 from 'Fundacao para a Ciencia e Tecnologia' (FCT), Portugal

The Acculturated Brain

Recent decades have been marked by a steadily increasing emphasis on neural determinants of behavior. Concerns with socio-cultural processes have simultaneously been diminished. Given the significance of this shift toward a cortical explanation of human behavior-in terms of both the direction of research in psychology and the implications of this research for social practices and policy-critical reflection is essential. In particular, when significant conceptual flaws are brought into focus, we find good reason to reconsider the significance of sociocultural process. And, when we take into account major vistas of neuropsychological research, the conclusion becomes evident that not only is human action unintelligible in terms of neural activity, but the brain primarily functions in the service of cultural process. To be sure, cortical functioning may both enable and limit human activity. However, given the enormous variation in human conduct, and the dependency of such conduct on the generation of cultural meaning, the most promising conclusion, both for research and for societal practice, is to view the brain chiefly as an instrument for achieving socially originated ends. This is not to argue against inquiry into brain functioning, but to be more judicious about the domains of its utility, and critical in terms of what it offers for understanding human action