Biomaterial Database

Characterization of Pneumocystis carinii PHR1, a pH-regulated gene important for cell wall Integrity. 2001

T J Kottom, and C F Thomas, and A H Limper

Thoracic Diseases Research Unit, Division of Pulmonary, Critical Care and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA.

Pneumocystis carinii remains an important opportunistic fungal pathogen causing life-threatening pneumonia in patients with AIDS and malignancy. Currently, little is known about how the organism adapts to environmental stresses and maintains its cellular integrity. We recently discovered an open reading frame approximately 600 bp downstream of the region coding GSC-1, a gene mediating beta-glucan cell wall synthesis in P. carinii. The predicted amino acid sequence of this new gene, termed P. carinii PHR1, exhibited 38% homology to Saccharomyces cerevisiae GAS1, a glycosylphosphatidylinositol-anchored protein essential to maintaining cell wall integrity, and 37% homology to Candida albicans PHR1/PHR2, pH-responsive genes encoding proteins recently implicated in cross-linking beta-1,3- and beta-1,6-glucans. In view of its homology to these related fungal genes, the pH-dependent expression of P. carinii PHR1 was examined. As in C. albicans, P. carinii PHR1 expression was repressed under acidic conditions but induced at neutral and more alkaline pH. PHR1-related proteins have been implicated in glucan cell wall stability under various environmental conditions. Although difficulties with P. carinii culture and transformation have traditionally limited assessment of gene function in the organism itself, we have successfully used heterologous expression of P. carinii genes in related fungi to address functional correlates of P. carinii-encoded proteins. Therefore, the potential role of P. carinii PHR1 in cell wall integrity was examined by assessing its ability to rescue an S. cerevisiae gas1 mutant with absent endogenous Phr1p-like activity. Interestingly, P. carinii PHR1 DNA successfully restored proliferation of S. cerevisiae gas1 mutants under lethal conditions of cell wall stress. These results indicate that P. carinii PHR1 encodes a protein responsive to environmental pH and capable of mediating fungal cell wall integrity.

UI	MeSH Term	Description	Entries
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011010	Pneumocystis	A genus of ascomycetous FUNGI, family Pneumocystidaceae, order Pneumocystidales. It includes various host-specific species causing PNEUMOCYSTIS PNEUMONIA in humans and other MAMMALS.	Pneumocysti
D002473	Cell Wall	The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.	Cell Walls,Wall, Cell,Walls, Cell
D004255	Deoxyribodipyrimidine Photo-Lyase	An enzyme that catalyzes the reactivation by light of UV-irradiated DNA. It breaks two carbon-carbon bonds in PYRIMIDINE DIMERS in DNA.	DNA Photolyase,DNA Photoreactivating Enzyme,Photoreactivating Enzyme,Photoreactivation Enzyme,DNA Photolyases,Deoxyribodipyrimidine Photolyase,Photolyase,Photolyases,Deoxyribodipyrimidine Photo Lyase,Photo-Lyase, Deoxyribodipyrimidine,Photolyase, DNA,Photolyase, Deoxyribodipyrimidine,Photolyases, DNA,Photoreactivating Enzyme, DNA
D005656	Fungal Proteins	Proteins found in any species of fungus.	Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D006863	Hydrogen-Ion Concentration	The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH	pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001051	Apoenzymes	The protein components of enzyme complexes (HOLOENZYMES). An apoenzyme is the holoenzyme minus any cofactors (ENZYME COFACTORS) or prosthetic groups required for the enzymatic function.	Apoenzyme
D015966	Gene Expression Regulation, Fungal	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.	Fungal Gene Expression Regulation,Regulation of Gene Expression, Fungal,Regulation, Gene Expression, Fungal