title: ALL2, a Homologue of ALL1, Has a Distinct Role in Regulating pH Homeostasis in the Pathogen Cryptococcus neoformans.
abstract: Cryptococcus neoformans is a facultative intracellular fungal pathogen that has a polysaccharide capsule and causes life-threatening meningoencephalitis. Its capsule, as well as its ability to survive in the acidic environment of the phagolysosome, contributes to the pathogen's resilience in the host environment. Previously, we reported that downregulation of allergen 1 (ALL1) results in the secretion of a shorter, more viscous exopolysaccharide with less branching and structural complexity, as well as altered iron homeostasis. Now, we report on a homologous coregulated gene, allergen 2 (ALL2). ALL2's function was characterized by generating null mutants in C. neoformans. In contrast to ALL1, loss of ALL2 attenuated virulence in the pulmonary infection model. The all2Δ mutant shed a less viscous exopolysaccharide and exhibited higher sensitivity to hydrogen peroxide than the wild type, and as a result, the all2Δ mutant was more resistant to macrophage-mediated killing. Transcriptome analysis further supported the distinct function of these two genes. Unlike ALL1's involvement in iron homeostasis, we now present data on ALL2's unique function in maintaining intracellular pH in low-pH conditions. Thus, our data highlight that C. neoformans, a human-pathogenic basidiomycete, has evolved a unique set of virulence-associated genes that contributes to its resilience in the human niche.
authors.affiliation: Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Neena
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Medicine (Infectious Diseases), Stony Brook University, Stony Brook, New York, USA.
authors.forename: Tejas
authors.initials: T
authors.lastname: Bouklas
authors.affiliation: Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Medicine (Infectious Diseases), Stony Brook University, Stony Brook, New York, USA.
authors.forename: Avanish K
authors.initials: AK
authors.lastname: Varshney
authors.affiliation: Department of Microbiology and Molecular Genetics, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Erika P
authors.initials: EP
authors.lastname: Orner
authors.affiliation: Department of Medicine (Infectious Diseases), Stony Brook University, Stony Brook, New York, USA Department of Microbiology and Molecular Genetics, Stony Brook University, Stony Brook, New York, USA bettina.fries@stonybrookmedicine.edu.
authors.forename: Bettina C
authors.initials: BC
authors.lastname: Fries
mesh_terms: D000485:Allergens / Q000235:genetics* / Q000502:physiology; D000818:Animals; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008168:Lung / Q000382:microbiology; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D014617:Vacuoles / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D000485:Allergens; D005656:Fungal Proteins; D037521:Virulence Factors; D006861:Hydrogen Peroxide