Balancing Stability and Flexibility within the Genome of the Pathogen Cryptococcus neoformans

Over the last 30 years, the growing immunocompromised population has created fertile ground for opportunistic pathogens, particularly those from the Kingdom Fungi. While the range of fungal species causing infections is increasing, there remain three key culprits [1]. Firstly, the ascomycete yeast Candida albicans is responsible for the greatest number of fungal infections, particularly those acquired in a hospital setting. Secondly, the mould Aspergillus fumigatus, also an ascomycete, has become a cause of high mortality, particularly in transplant patients and those with hematological diseases. Finally, the basidiomycete yeast Cryptococcus neoformans has become a scourge of AIDS patients, accounting for an estimated 624,000 deaths per annum [2]. The genomes of C. albicans and A. fumigatus were published in 2004 [3] and 2005 [4] respectively, and the C. neoformans var. neoformans genome was published in 2005 [5]. Excitingly, the var. grubii genome, the variety responsible for the majority of infections [6], is nearing publication [G. Janbon, personal communication]. The analysis of these C. neoformans sequences, coupled with earlier karyotypic analyses, has uncovered a paradox: a pathogen with a highly stable genome that appears to have the capacity to undergo gross chromosomal rearrangement when required. This ‘‘flexible stability’’ could potentially represent an adaptive strategy supporting the opportunistic nature of this important pathogen.