“Overall, the paper implies that a whole genome approach will be essential to understanding the biology of the pathogen and important in developing long term effective treatments”

Our paper is highly cited as it represents the first whole-genome view of the important emerging fungal pathogen Cryptococcus neoformans. The work, which has contributions from a wide variety of C. neoformans scientists, uncovers the blueprint of an environmental pathogen which contains niche adaptations to its external environment as well as to survival in the human host. In addition, the paper describes an unexpected complexity at the level of gene structure and gene regulation. Finally, by elucidating the genomes of two close relatives of differing virulence properties, the paper catalogs the genetic differences that may underlie these differences in pathogenicity. Overall, the paper implies that a whole genome approach will be essential to understanding the biology of the pathogen and is important in the development of long-term effective treatments.

The paper describes the entire genetic blueprint of C. neoformans, from which a number of important discoveries have been made and .which will provide a foundation and starting point for the discovery of many more. It places an essential and valuable tool in the hands of researchers studying the organism and also those studying fungal pathogens in general. Those interested in genome evolution, gene structure, and gene regulation will find much new information contained within the data emanating from the paper.

The paper, the data underlying it, and the analyses contained therein, provide the informational blueprint of this important human pathogen. The data highlights a number of the adaptations of C. neorformans to cope with life in its external environment and the strategies it has developed to evade the immune response of the human host. These adaptations can then be compared with those of other fungal pathogens to help understand the molecular basis of pathogenicity and also to help develop broad spectrum antifungals, or conversely, pathogen-specific treatments.

I became involved in this research as Cryptococcus became a targeted organism for whole genome studies by NIAID and when TIGR and Stanford were chosen as the participating centers. During the project, it was discovered that DNA from two highly related strains differing in virulence were being sequenced. This provided additional challenges in terms of separating and assembling the data from these two strains. Once completed, however, the combination of their similarity and also the differences contained between the strains, provided invaluable information regarding the genetic basis of virulence in this organism.

The social implications of the research are primarily that a new and valuable asset has been placed in the hands of the researchers working on this important pathogen. This greatly expands the knowledge base, attracts new researchers to the field, and will expedite ongoing work in searching for effective treatments for this important emerging fungal pathogen.