Malassezia responds to environmental pH signals through the conserved Rim/Pal pathway.

Autor:	Pianalto KM; Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA., Telzrow CL; Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA., Brown Harding H; Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA., Brooks JT; Department of Physics and Astronomy, University of North Carolina, Chapel Hill, North Carolina, USA., Granek JA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA., Gushiken-Ibañez E; Section of Immunology at Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., LeibundGut-Landmann S; Section of Immunology at Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Heitman J; Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, USA., Ianiri G; Department of Agricultural, Environmental and Food Sciences, Università degli Studi del Molise, Campobasso, Italy., Alspaugh JA; Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.; Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	MBio [mBio] 2024 Oct 16; Vol. 15 (10), pp. e0206024. Date of Electronic Publication: 2024 Aug 27.
DOI:	10.1128/mbio.02060-24
Abstrakt:	During mammalian colonization and infection, microorganisms must be able to rapidly sense and adapt to changing environmental conditions including alterations in extracellular pH. The fungus-specific Rim/Pal signaling pathway is one process that supports microbial adaptation to alkaline pH. This cascading series of interacting proteins terminates in the proteolytic activation of the highly conserved Rim101/PacC protein, a transcription factor that mediates microbial responses that favor survival in neutral/alkaline pH growth conditions, including many mammalian tissues. We identified the putative Rim pathway proteins Rim101 and Rra1 in the human skin colonizing fungus Malassezia sympodialis . Gene deletion by transconjugation and homologous recombination revealed that Rim101 and Rra1 are required for M. sympodialis growth at higher pH. In addition, comparative transcriptional analysis of the mutant strains compared to wild-type suggested mechanisms for fungal adaptation to alkaline conditions. These pH-sensing signaling proteins are required for optimal growth in a murine model of atopic dermatitis, a pathological condition associated with increased skin pH. Together, these data elucidate both conserved and phylum-specific features of microbial adaptation to extracellular stresses.IMPORTANCEThe ability to adapt to host pH has been previously associated with microbial virulence in several pathogenic fungal species. Here we demonstrate that a fungal-specific alkaline response pathway is conserved in the human skin commensal fungus Malassezia sympodialis ( Ms ). This pathway is characterized by the pH-dependent activation of the Rim101/PacC transcription factor that controls cell surface adaptations to changing environmental conditions. By disrupting genes encoding two predicted components of this pathway, we demonstrated that the Rim/Pal pathway is conserved in this fungal species as a facilitator of alkaline pH growth. Moreover, targeted gene mutation and comparative transcriptional analysis support the role of the Ms Rra1 protein as a cell surface pH sensor conserved within the basidiomycete fungi, a group including plant and human pathogens. Using an animal model of atopic dermatitis, we demonstrate the importance of Ms Rim/Pal signaling in this common inflammatory condition characterized by increased skin pH. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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