title: The transcriptional response of Cryptococcus neoformans to ingestion by Acanthamoeba castellanii and macrophages provides insights into the evolutionary adaptation to the mammalian host.
abstract: Virulence of Cryptococcus neoformans for mammals, and in particular its intracellular style, was proposed to emerge from evolutionary pressures on its natural environment by protozoan predation, which promoted the selection of strategies that allow intracellular survival in macrophages. In fact, Acanthamoeba castellanii ingests yeast cells, which then can replicate intracellularly. In addition, most fungal factors needed to establish infection in the mammalian host are also important for survival within the amoeba. To better understand the origin of C. neoformans virulence, we compared the transcriptional profile of yeast cells internalized by amoebae and murine macrophages after 6 h of infection. Our results showed 656 and 293 genes whose expression changed at least 2-fold in response to the intracellular environments of amoebae and macrophages, respectively. Among the genes that were found in both groups, we focused on open reading frame (ORF) CNAG_05662, which was potentially related to sugar transport but had no determined biological function. To characterize its function, we constructed a mutant strain and evaluated its ability to grow on various carbon sources. The results showed that this gene, named PTP1 (polyol transporter protein 1), is involved in the transport of 5- and 6-carbon polyols such as mannitol and sorbitol, but its presence or absence had no effect on cryptococcal virulence for mice or moth larvae. Overall, these results are consistent with the hypothesis that the capacity for mammalian virulence originated from fungus-protozoan interactions in the environment and provide a better understanding of how C. neoformans adapts to the mammalian host.
authors.affiliation: Laboratório de Biologia Molecular, CEL/IB, Universidade de Brasília, Brasília, DF, Brazil. lorena.bio@gmail.com
authors.forename: Lorena da S
authors.initials: Lda S
authors.lastname: Derengowski
authors.forename: Hugo Costa
authors.initials: HC
authors.lastname: Paes
authors.forename: Patrícia
authors.initials: P
authors.lastname: Albuquerque
authors.forename: Aldo Henrique F P
authors.initials: AH
authors.lastname: Tavares
authors.forename: Larissa
authors.initials: L
authors.lastname: Fernandes
authors.forename: Ildinete
authors.initials: I
authors.lastname: Silva-Pereira
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D048248:Acanthamoeba castellanii / Q000382:microbiology*; D000220:Adaptation, Biological / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003453:Cryptococcosis / Q000276:immunology / Q000382:microbiology*; D003455:Cryptococcus neoformans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D005260:Female; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D054884:Host-Pathogen Interactions; D007700:Kinetics; D007814:Larva / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009036:Moths / Q000382:microbiology; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis; D010641:Phenotype; D013045:Species Specificity; D014158:Transcription, Genetic; D059467:Transcriptome; D014774:Virulence