Pneumocystis jirovecii is a microscopic fungus causing severe pneumonia in immuno-compromised patients (AIDS, transplantation recipients, leukemia, etc.). In the absence of an in vitro culture system, the biology of this fungus remains poorly known.
Thanks to recent technical developments, we have sequenced and are currently analyzing P. jirovecii genome (see Collaborative Research). Comparative genomics revealed the loss of specific pathways in Pneumocystis species. These findings strongly suggest that these fungi are obligate biotrophs of mammalian lungs, i.e. pathogens retrieving their nutriments without killing the cells of their host.
Comparative genomics were also used to investigate the mode of reproduction of P. jirovecii, a crucial feature since sexuality occurs within the host and appears obligatory. These analyses led to the working hypothesis that the mode of reproduction of Pneumocystis species is primary homothallism, i.e. that both sexes are present in each strain.
In the absence of efficient therapy to replace antifolates, we look for new therapeutic targets. We determine the function of new potential drug target genes by their expression in model yeast Saccharomyces cerevisiae (the picture to the left shows a green-fluorescent P. jirovecii protein localized in the nuclear membrane of S. cerevisiae, the other picture shows S. cerevisiae nuclear and mitochondrial DNA stained in blue with DAPI). These recombinant strains are also used to search for new drugs.