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Fungi are exposed to broadly fluctuating environmental conditions, to which adaptation is crucial for their survival. An ability to respond to a wide pH range, in particular, allows them to cope with rapid changes in their extracellular settings. PacC/Rim signaling elicits the primary pH response in both model and pathogenic fungi and has been studied in multiple fungal species. In the predominant human pathogenic fungi, namely, Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, this pathway is required for many functions associated with pathogenesis and virulence. Aspects of this pathway are fungus specific and do not exist in mammalian cells. In this review, we highlight recent advances in our understanding of PacC/Rim-mediated functions and discuss the growing interest in this cascade and its factors as potential drug targets for antifungal strategies. We focus on both conserved and distinctive features in model and pathogenic fungi, highlighting the specificities of PacC/Rim signaling in C. albicans, A. fumigatus, and C. neoformans. We consider the role of this pathway in fungal virulence, including modulation of the host immune response. Finally, as now recognized for other signaling cascades, we highlight the role of pH in adaptation to antifungal drug pressure. By acting on the PacC/Rim pathway, it may therefore be possible (i) to ensure fungal specificity and to limit the side effects of drugs, (ii) to ensure broad-spectrum efficacy, (iii) to attenuate fungal virulence, (iv) to obtain additive or synergistic effects with existing antifungal drugs through tolerance inhibition, and (v) to slow the emergence of resistant mutants. 相似文献
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Ambient pH gene regulation in fungi: making connections 总被引:1,自引:0,他引:1
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Susana Negrete-Urtasun Wolfgang Reiter Eliecer Diez Steven H. Denison Joan Tilburn Eduardo A. Espeso Miguel A. Peñalva & Herbert N. Arst Jr 《Molecular microbiology》1999,34(5):1149-1149
Completing the molecular analysis of the six pal genes of the ambient pH signal transduction pathway in Aspergillus nidulans , we report the characterization of palC and palH . The derived translation product of palH contains 760 amino acids with prediction of seven transmembrane domains in its N-terminal moiety. Remarkably, a palH frameshift mutant lacking just over half the PalH protein, including almost all of the long hydrophilic region C-terminal to the transmembrane domains, retains some PalH function. The palC -derived translation product contains 507 amino acids, and the null phenotype of a frameshift mutation indicates that at least one of the C-terminal 142 residues is essential for function. Uniquely among the A. nidulans pH-signalling pal genes, palC appears to have no Saccharomyces cerevisiae homologue, although it does have a Neurospora crassa expressed sequence tag homologue. In agreement with findings for the palA , palB and palI genes of this signalling pathway, levels of the palC and palH mRNAs do not appear to be pH regulated. 相似文献
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The infection structures, trophism, and ecological character of nematophagous fungi are reviewed in this article on the basis
of data extracted from the literature and the most recent experiments conducted in this area. Traditionally, nematophagous
fungi are classified into four groups according to their modes of attacking nematodes: nematode-trapping fungi using adhesive
or mechanical hyphal traps, endoparasitic fungi using their spores, eggparasitic fungi invading nematode eggs or females with
their hyphal tips, and toxin-producing fungi immobilizing nematodes before invasion. In the present review, we focus on the
first two groups. The living strategies of these nematophagous fungi depend on the diversity of their infection structures,
such as different traps and spore types, which determine the modes of infecting nematodes. The diversity of trophic modes
of nematophagous fungi is an important prerequisite for fungal survival and activity in soil. The abundance and activity of
Hirsutella rhossiliensis and H. minnesotensis, representatives of endoparasites and potential biocontrol agents against nematodes, are highly dependent on environmental
factors. Comprehensive understanding of the survival and activity of nematophagous fungi in soil is fundamental for the exploitation
of these fungi as successful biocontrol agents. 相似文献
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Mutual independence of alkaline‐ and calcium‐mediated signalling in Aspergillus fumigatus refutes the existence of a conserved druggable signalling nexus
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Omar Loss Margherita Bertuzzi Yu Yan Natalie Fedorova Bethany L. McCann Darius Armstrong‐James Eduardo A. Espeso Nick D. Read William C. Nierman Elaine M. Bignell 《Molecular microbiology》2017,106(6):861-875