Transcriptomics of the Fungal Pathogens, Focusing on Candida albicans

The past century brought the availability of vaccines and antibiotics, leading to a dramatic fall in mortalities caused by infectious diseases. This led to the assumption that infectious disease has been defeated by medicine. In 1969 the United States Surgeon General actually claimed that “we can close the book on infectious diseases”. However, today we know that this assumption was naïve, not taking into account that evolution is a constant motor in adapting the existing organisms to changing environmental conditions, including the adaptation of pathogens to changes in the host. Today nearly 25% of the annual deaths world-wide are directly related to pathogens (Morens et al. 2004). This can be attributed to the appearance of new diseases, like HIV, SARS or West Nile Virus, but also to an increase of resistance to antibiotics in pathogens thought to be defeated, like Mycobacterium tuberculosis or Staphylococcus and Enterococcus strains. In addition the progress in medical care results in a large proportion of immune-deficient patients and consequently in an increase in opportunistic infections. Especially fungi have gained an infamous reputation during recent decades as being highly detrimental to patients with haematologiconcologic diseases, neutropenia or after organ transplantation. A review of the current literature identified 1415 species as known to be pathogenic to humans, including 538 bacteria and 307 fungi (Cleaveland et al. 2001). The fungi are a large group of diverse eukaryotic organisms. Only about 74 000 to 120 000 of the estimated 1.5×10(6) existing species of fungi have been described. Of the approximately 300 fungal species that are known to cause human infections, the most commonly observed live threatening systemic infections are caused by opportunistic infections of Candida species or Aspergilli. Therefore the major scientific interest with regard to fungal pathomechanisms has focused on these organisms in the past decade. The early availability of the genome sequence of Candida albicans (the first assembly of the genome sequence was publicly available in 2000, at http://www-sequence.stanford.edu/group/candida),the availability of molecular tools and the use of Saccharomyces cerevisiae as a model for many characteristics of C. albicans relevant for pathogenesis (including morphogenesis and signalling pathways involved in stress response) resulted in a major body of work concerning this opportunistic fungal pathogen (Berman and Sudbery 2002; Braun et al. 2005; Jones et al. 2004). Until 2004 C. albicans was actually the only fungal pathogen on which genome-wide transcriptomics using arrays had been published. The sequences of other pathogenic fungi or the tools required for genome-wide transcriptomics had not been available to the public until then. However, a major body of molecular work has been performed on other opportunistic fungal pathogens, including C. glabrata, C. parapsylosis, C. tropicalis, Cryptococcus neoformans and Aspergillus species, where Aspergillus fumigatus is leading the clinically relevant species, as well as on the genera of primary fungal pathogens, including Blastomyces, Coccidioides, Histoplasma and Paracoccidioides. Due to the advancement of Candida albicans transcriptomics this chapter mainly focuses on this organism and only briefly touches the current work on other fungal pathogens.