Scientists have sequenced the genome of the
fungus1 Pneumocystis jirovecii, an
advancement2 that could help identify new targets for drugs to treat and prevent Pneumocystis
pneumonia3, a common and often deadly infection in
immunocompromised(免疫功能不全的) patients. The study will be published on December 26, 2012 in mBio®, the online open-access journal of the American Society for Microbiology. The organism cannot yet be
isolated4 and grown for study in the laboratory, so details about Pneumocystis pneumonia, the biology of P. jirovecii, and its pathogenicity are hard to come by. The genome sequence represents a wealth of new information for doctors and researchers tackling this disease. Pneumocystis pneumonia is an opportunistic infection that strikes most often in individuals with diminished immune systems. The corresponding author of the study in mBio®, Philippe Hauser of the Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland, says the disease gained importance in the 1980s.
"Recognized first among malnourished infants, P. jirovecii pneumonia became a public issue with the
advent5 of the HIV epidemic," says Hauser. Today, the disease most commonly affects HIV-infected persons who are
unaware6 of their status as well as solid organ transplant
recipients7 and patients with hemato-oncologic or autoimmune diseases. Since the organism cannot be grown in the lab for study, researchers have long made do with studying P. jirovecii's lab-friendly relatives, species that infect animals and plants, in order to explore the secrets of the human disease.
"It is obviously better to study [P. jirovecii's]
genes8 rather that those of Pneumocystis species from animal models. The genome has both medical and
evolutionary9 interests for the scientific community," says Hauser.
Under normal circumstances, scientists sequencing the genome of a microorganism simply extract
DNA10 from thick cultures of cells they grow in the lab. Since they were unable to grow P. jirovecii cells for their genomic DNA, Hauser and his colleagues took a different approach. They took a sample of bronchoalveolar lavage fluid from an individual infected with Pneumocystis pneumonia, then concentrated the P. jirovecii cells using immuno-precipitation and created copies of the DNA in the sample using a technique called
random11 DNA
amplification12. This mixture of DNA
strands13, from P. jirovecii, human, and other microbes from the lungs of the infected patient, was then sequenced using high throughput technologies.