Research Article: Environmental pH modulation by pathogenic fungi as a strategy to conquer the host

Date Published: February 23, 2017

Publisher: Public Library of Science

Author(s): Slavena Vylkova, Deborah A. Hogan.


Partial Text

In fungi, the adaptive responses induced by changes in ambient pH have been extensively studied in model organisms. For example, the response to weak acid stress has been characterized in Saccharomyces cerevisiae [5], while the role of the Pal/Rim alkaline response pathway, one of the most specialized and conserved signaling cascades in fungi, has been delineated in S. cerevisiae, Aspergillus nidulans, Yarrowia lipolytica, and several fungal pathogens [6–8]. The mechanisms of pH sensing and adaptation in fungi have been reviewed elsewhere [9–11].

Another aspect of pH regulation is the ability of microorganisms to actively modify the pH of their environment. Fungi can achieve this by secreting acids or alkali. The ability of fungi to secrete natural organic acids (such as butyrate, oxalate, malate, citrate, gluconate, and succinate) is well utilized in the industry, particularly with nonpathogenic Aspergillus sp. and Rhizopus sp. The magnitude of pH change depends on the nutrient availability, the organic acids being produced, and on the ability of the fungus to remove ammonium ions from ammonium sulfate salt or to excrete H+-ions as a byproduct of NH4+ assimilation [12, 13]. Acidifying fungi can also raise extremely low pH levels to a favorable level.

Environmental alkalinization in fungi is common yet not a well-understood phenomenon. Often, this process is mediated by ammonia, a multifunctional biological molecule with diverse roles in eukaryotes. In fungi, it supports communication between colonies in S. cerevisiae [20], aging of surface-ripened cheeses by Y. lipolytica and Debaryomyces hansenii [21], and expression of pectin lyase, a key virulence factor in Colletotrichum sp. [22], among other functions.

Fungi regulate the production of ammonia depending on environmental cues. Ammonia production by M. anisopliae is tightly regulated by amino acids, a signal for the presence of proteinaceous nutrients in the environment. M. anisopliae grown in media containing low levels of single amino acids yields higher levels of ammonia than when amino acids are abundant, implying either induction of catabolite repressible enzyme(s) or regulation of enzyme activity via substrate inhibition [28]. Generation of ammonia by N. crassa and A. fumigatus is a loosely regulated process triggered by nutrient deprivation [36]. Presence of glucose in the environment represses the process, presumably due to the metabolic switch from gluconeogenesis to glycolysis or repression of deaminases and ammonia transporters. It is also possible that the higher growth rate in the presence of glucose allows for complete utilization of ammonia released from amino acid catabolism.

Many fungal pathogens modulate environmental pH as a means to escape host immune responses, facilitate destruction of the host tissues, and/or stimulate reproduction. Most fungi inhabit mildly acidic environments, such as soil, plant, and animal surfaces. On the other hand, for some fungi, such as the phytopathogens C. gloeosporioides and M. oryzae, acidic pH favors fungal colonization and invasion [12, 28]. The mildly acidic pH of the plant surface favors both germination of attached conidia and rapid differentiation of the germ tube into a specialized cell named appressorium. Once the appressorium penetrates the plant tissues, the fungus switches to necrotrophic development, associated with rapid ammonia release and increase in environmental pH, which triggers the expression of virulence factors [13, 22, 28, 37]. Thus, the acidic environment serves as a signal in this fungus to switch from saprotrophic to necrotrophic growth and damage the host (Fig 1).