Researchers at the National Institutes of Health Clinical Center, in collaboration with extramural organizations, have sequenced nearly the entire genome of human, mouse and rat Pneumocystis. This organism causes a life-threatening pneumonia in immunosuppressed hosts. Pneumocystis was one of the first infections that led to the initial recognition of the HIV/AIDS epidemic.
It has been responsible for thousands of deaths over the past 30 years and remains a significant risk in the HIV/AIDS population as well as in transplant recipients and other immunosuppressed patients. Findings were published in Nature Communications. NIH scientists collaborated with investigators from the Broad Institute and Leidos, Inc.
Through analysis of the genomes, researchers now better understand where the organism lives and how it avoids elimination by its hosts’ immune system. The high quality of the genomes allowed not only identification of metabolic pathways that are critical to the growth and survival of the organism, but also recognition that a large number of pathways that are present in other closely related fungi are absent from Pneumocystis. These pathways likely disappeared as Pneumocystis evolved to become highly dependent on its mammalian host to stay alive.
“Our long term goal is to learn more about human Pneumocystis infection and to decrease its impact on immunosuppressed humans. This study is an important step in that direction” said Joseph Kovacs, M.D., senior investigator and head of the Acquired Immunodeficiency Syndrome Section for the NIH Clinical Center Critical Care Medicine Department.
“Having the genome information helped us recognize the unusual biology of Pneumocystis and how it co-exists with its mammalian hosts. It also gives researchers insight into why they’ve been unable to reproducibly grow the organism in lab cultures thus far,” said Liang Ma, M.D., staff scientist in the NIH Clinical Center Critical Care Medicine Department and first author of the paper.
The research has mapped out a clearer picture of these genomes than any prior studies. The team’s effort has resulted in high-quality, near chromosomal draft genomes, which is the highest level of genomic mapping. This detailed description of the genes that are present or missing should facilitate attempts to culture the organism, a critical milestone in Pneumocystis research.
Culturing could allow for screening of a large number of drugs to speed up identification of new treatments for Pneumocystis pneumonia, and potentially allow for genetic manipulation to modify individual genes and see what impact they have on organism growth and on its harmful impact to the host.