pH Response Pathways in Fungi: Adapting to Host-derived and Environmental Signals

Abstract

Microorganisms are significantly affected when the ambient pH of their environment changes. They must therefore be able to sense and respond to these changes in order to survive. Previous investigators have studied various fungal species to define conserved pH-responsive signaling pathways. One of these pathways, known as the Pal/Rim pathway, is activated in response to alkaline pH signals, ultimately targeting the PacC/Rim101 transcription factor. Although the central signaling components are conserved among divergent filamentous and yeast-like fungi, there is some degree of signaling specificity between fungal species. This specificity exists primarily in the downstream transcriptional targets of this pathway, likely allowing differential adaptation to species-specific environmental niches. In this review, the role of the Pal/Rim pathway in fungal pH response is discussed. Also highlighted are functional differences present in this pathway among human fungal pathogens, differences that allow these specialized microorganisms to survive in the various micro-environments of the infected human host.

The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane

“…For instance, fungi that grow over a wide pH range, such as Saccharomyces cerevisiae, Candida albicans, and Aspergillus nidulans, adapt to alkaline conditions via the Rim101 pathway [1][2][3]. For adaptation to external alkalization, these fungi activate the Rim101 pathway to induce alkaline-responsive genes, which encode for secreted enzymes, cell wall proteins, and proteins required for ion homeostasis [4][5][6][7].…”

“…For adaptation to external alkalization, these fungi activate the Rim101 pathway to induce alkaline-responsive genes, which encode for secreted enzymes, cell wall proteins, and proteins required for ion homeostasis [4][5][6][7]. For pathogenic fungi, adaptation to external pH is critical for growth and pathogenicity in the host organisms [2,3]. Therefore, understanding the mechanism of this adaptation is an important aspect of drug development and agriculture, as well as basic biology.…”

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

“…In fungi, the response to pH change is regulated by the Pal/Rim pathway, activated in neutral to alkaline pH with a downstream transcription factor effector, PacC/Rim101 (1026,1027). The pacC/pac1 homolog of T. reesei, T. atroviride, and T. virens (TR_120698, TA_78054, and TV_40391) encodes a protein with three C2H2 zinc fingers in the N-terminal region, as is the case in N. crassa and Aspergillus spp.…”

pH Signaling in Human Fungal Pathogens: a New Target for Antifungal Strategies

“…The genes and activities controlled by PacC/ Rim101 in the model organisms A. nidulans, S. cerevisiae, and Y. lipolytica can be classified into several functional categories, including siderophore biosynthesis and iron or copper metabolism, ion homeostasis, the production of extracellular alkaline or acidic proteases or permeases, the production of enzymes involved in the synthesis of exported metabolites, membrane or cell wall biosynthesis and remodeling, sporulation, mating, dimorphism, invasive growth, and biofilm formation (12)(13)(14)(15)(65)(66)(67)(68)(69). In pathogenic fungi, most of these functions are related to pathogenesis and virulence.…”