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

Species Distribution and Susceptibility to Azole Antifungals of Candida Bloodstream Isolates from Eight University Hospitals in Korea

PURPOSE: The incidence of Candida bloodstream infections (BSI) has increased over the past two decades. The rank order of occurrence and the susceptibility to antifungals of the various Candida species causing BSI are important factors driving the establishment of empirical treatment protocols; however, very limited multi-institutional data are available on Candida bloodstream isolates in Korea. MATERIALS AND METHODS: We investigated the susceptibility to azole antifungals and species distribution of 143 Candida bloodstream isolates recovered from eight university hospitals over a six-month period. Minimal inhibitory concentrations (MICs) of fluconazole, itraconazole, and voriconazole for each isolate were determined by the broth microdilution method of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: The Candida species recovered most frequently from the blood cultures was C. albicans (49%), followed by C. parapsilosis (22%), C. tropicalis (14%), and C. glabrata (11%). The MIC ranges for the Candida isolates were 0.125 to 64 microg/mL for fluconazole, 0.03 to 2 microg/mL for itraconazole, and 0.03 to 1 microg/mL for voriconazole. Overall, resistance to fluconazole was found in only 2% of the Candida isolates (3/143), while the dose-dependent susceptibility was found in 6% (8/143). The resistance and dose-dependent susceptibility of itraconazole were found in 4% (6/143) and 14% (20/143) of the isolates, respectively. All bloodstream isolates were susceptible to voriconazole (MIC, < or = 1 microg/mL). CONCLUSION: Our findings show that C. albicans is the most common cause of Candida-related BSI, followed by C. parapsilosis, and that the rates of resistance to azole antifungals are still low among bloodstream isolates in Korea.ope

Chronic fungal meningitis caused by Aureobasidium proteae

We present a case of chronic meningitis due to the mold Aureobasidium proteae. Clinical features, the disease course, as well as the diagnostic methods and optimal treatment options are discussed. This case confirms the neuroinvasiveness of A. proteae and introduces it as a new human pathogen

Polymeric micelles anchored with TAT for delivery of antibiotics across the blood-brain barrier

10.1002/bip.20998Biopolymers - Peptide Science Section905617-62