Using in vivo imaging, we identified cryptic sites of infection and persistence of C. albicans in the gall bladder during otherwise effective antifungal treatment. Bile appears to directly interfere with antifungal activity.
The opportunistic fungal pathogen Candida albicans has a remarkable ability to adapt to unfavorable environments by different mechanisms, including microevolution. For example, a previous study has shown that passaging through the murine spleen can cause new phenotypic characteristics. Since the murine kidney is the main target organ in murine Candida sepsis and infection of the spleen differs from the kidney in several aspects, we tested whether C. albicans SC5314 could evolve to further adapt to infection and persistence within the kidney. Therefore, we performed a long-term serial passage experiment through the murine kidney of using a low infectious dose. We found that the overall virulence of the commonly used wild type strain SC5314 did not change after eight passages and that the isolated pools showed only very moderate changes of phenotypic traits on the population level. Nevertheless, the last passage showed a higher phenotypic variability and a few individual strains exhibited phenotypic alterations suggesting that microevolution has occurred. However, the majority of the tested single strains were phenotypically indistinguishable from SC5314. Thus, our findings indicate that characteristics of SC5314 which are important to establish and maintain kidney infection over a prolonged time are already well developed.
Transcriptional profiling is a powerful tool to investigate the interplay between pathogens and their hosts. For several pathogenic fungi, like Candida albicans, genome-wide microarrays are now available, and alternative methods, such as Serial Analysis of Gene Expression (SAGE) or RNASeq, are becoming increasingly widespread. In other chapters of this book, in vitro models for studying fungal infections are described. Here, we provide information on methods to isolate fungal RNA from these models and to investigate transcriptional changes during experimental infections. The protocols focus on C. albicans but are applicable to many other fungi with minor modifications.
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