Current insights into the biology and pathogenesis of Pneumocystis pneumonia

Key Points Pneumocystis pneumonia (PCP) remains the most prevalent opportunistic infection in patients with AIDS and is a significant cause of severe pneumonia in immunocompromised patients with cancer, organ transplant recipients or those receiving immunosuppressant medications. Pneumocystis is an intractable fungal pathogen classified phylogenetically with the Ascomycetes. Pneumocystis has pathways involved in cell-cycle control, signal transduction and metabolism that are analogous to the pathways in these yeast. Pneumocystis has a unique life cycle alternating between small trophic forms and cysts, which contain 2, 4 or 8 intracystic bodies. The airborne route of transmission is currently the favoured model for the spread of infection. Pneumocystis interacts with the lung epithelium and immune cells of the lower respiratory tract, resulting in inflammation, which is hazardous to the host. This is a complex interaction involving surface antigens of the organism and host surfactant proteins, adhesion molecules, macrophages, neutrophils, lymphocytes, and cytokine and chemokine responses. Drug targets for the treatment of PCP include metabolic pathways for dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), DNA and protein synthesis inhibition, sterol metabolism, cytochrome b complex and cell-wall construction through inhibition of the GSC1 glucan synthetase. Mutations in DHPS, DHFR, and cytochrome b have raised the concern of emerging resistance to the medications currently in use. The efforts of the Pneumocystis research community have contributed substantially to the current understanding of the complex biology of Pneumocystis and the intricate association with the host. Continued research is essential to continue investigating the biology of this organism in the hope of developing novel treatment strategies for PCP. Pneumonia caused by the fungus Pneumocystis is the most prevalent opportunistic infection in patients with AIDS. Here, Charles Thomas and Andrew Limper review the latest knowledge on the biology and pathogenesis of this opportunistic fungal pathogen. The fungal infection Pneumocystis pneumonia is the most prevalent opportunistic infection in patients with AIDS. Although the analysis of this opportunistic fungal pathogen has been hindered by the inability to isolate it in pure culture, the use of molecular techniques and genomic analysis have brought insights into its complex cell biology. Analysis of the intricate relationsh