Special Issue "Fungal Nutrition Assimilation Strategies and Pathogenicity"

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 July 2017)

Special Issue Editor

Guest Editor
Assoc. Prof. Julianne Djordjevic

Centre for Infectious Diseases and Microbiology, Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, NSW 2145, Australia
Website | E-Mail
Interests: mycology; fungal pathogenesis; Cryptococcus neoformans; Host-pathogen interaction; kinases; phosphate homeostasis; inositol polyphosphates; gene expression; cell biology; animal infection models; innate immune response; macrophages and monocytes

Special Issue Information

Dear Colleagues,

Invasive fungal infections are a major cause of morbidity and mortality globally, particularly in patients immunocompromised as a result of HIV infection or the administration of immunosuppressive medications to prevent solid organ, hematopoietic stem cell, or bone marrow transplant rejection. They are also a major cause of disease in plants and therefore threaten the stability of global crop production. The ability of fungi to obtain enough nutrients to support their growth within their host environments is a fundamental requirement for disease outcome. With only a limited repertoire of antifungal agents available, some of which are toxic, lack pan-fungal activity and/or are costly, and the emergence of drug resistance, fungal nutrient acquisition and biosynthetic pathways may therefore provide an alternative avenue to target for future drug development.

This Special Issue focuses on research, which advances our knowledge on how fungi synthesize or acquire sufficient nutrients for proliferation, virulence factor production and the establishment of infection. This research has largely been facilitated by technological advancement in targeted disruption within fungal genomes and the establishment of animal and cell models of fungal infection.

Dr. Julianne Djordjevic
Guest Editor

Manuscript Submission Information

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Keywords

  • molecular fungal pathogenesis
  • host-pathogen interaction
  • nutrient biosynthesis and acquisition
  • animal models
  • medical mycology
  • mycoses

Published Papers (5 papers)

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Research

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Open AccessArticle Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
Microorganisms 2017, 5(3), 49; https://doi.org/10.3390/microorganisms5030049
Received: 24 July 2017 / Revised: 16 August 2017 / Accepted: 18 August 2017 / Published: 23 August 2017
Cited by 3 | PDF Full-text (3063 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cryptococcus gattii is a human and animal pathogen that infects healthy hosts and caused the Pacific Northwest outbreak of cryptococcosis. The inhalation of infectious propagules can lead to internalization of cryptococcal cells by alveolar macrophages, a niche in which C. gattii cells can [...] Read more.
Cryptococcus gattii is a human and animal pathogen that infects healthy hosts and caused the Pacific Northwest outbreak of cryptococcosis. The inhalation of infectious propagules can lead to internalization of cryptococcal cells by alveolar macrophages, a niche in which C. gattii cells can survive and proliferate. Although the nutrient composition of macrophages is relatively unknown, the high induction of amino acid transporter genes inside the phagosome indicates a preference for amino acid uptake instead of synthesis. However, the presence of countable errors in the R265 genome annotation indicates significant inhibition of transcriptomic analysis in this hypervirulent strain. Thus, we analyzed RNA-Seq data from in vivo and in vitro cultures of C. gattii R265 to perform the reannotation of the genome. In addition, based on in vivo transcriptomic data, we identified highly expressed genes and pathways of amino acid metabolism that would enable C. gattii to survive and proliferate in vivo. Importantly, we identified high expression in three APC amino acid transporters as well as the GABA permease. The use of amino acids as carbon and nitrogen sources, releasing ammonium and generating carbohydrate metabolism intermediaries, also explains the high expression of components of several degradative pathways, since glucose starvation is an important host defense mechanism. Full article
(This article belongs to the Special Issue Fungal Nutrition Assimilation Strategies and Pathogenicity)
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Open AccessArticle Biotin Auxotrophy and Biotin Enhanced Germ Tube Formation in Candida albicans
Microorganisms 2016, 4(3), 37; https://doi.org/10.3390/microorganisms4030037
Received: 2 August 2016 / Revised: 7 September 2016 / Accepted: 14 September 2016 / Published: 21 September 2016
Cited by 3 | PDF Full-text (7878 KB) | HTML Full-text | XML Full-text
Abstract
Due to the increased number of immunocompromised patients, infections with the pathogen Candida albicans have significantly increased in recent years. C. albicans transition from yeast to germ tubes is one of the essential factors for virulence. In this study we noted that Lee’s [...] Read more.
Due to the increased number of immunocompromised patients, infections with the pathogen Candida albicans have significantly increased in recent years. C. albicans transition from yeast to germ tubes is one of the essential factors for virulence. In this study we noted that Lee’s medium, commonly used to induce filamentation, contained 500-fold more biotin than needed for growth and 40-fold more biotin than is typically added to growth media. Thus, we investigated the effects of excess biotin on growth rate and filamentation by C. albicans in different media. At 37 °C, excess biotin (4 µM) enhanced germ tube formation (GTF) ca. 10-fold in both Lee’s medium and a defined glucose-proline medium, and ca. 4-fold in 1% serum. Two biotin precursors, desthiobiotin and 7-keto-8-aminopelargonic acid (KAPA), also stimulated GTF. During these studies we also noted an inverse correlation between the number of times the inoculum had been washed and the concentration of serum needed to stimulate GTF. C. albicans cells that had been washed eight times achieved 80% GTF with only 0.1% sheep serum. The mechanism by which 1–4 µM biotin enhances GTF is still unknown except to note that equivalent levels of biotin are needed to create an internal supply of stored biotin and biotinylated histones. Biotin did not restore filamentation for any of the four known filamentation defective mutants tested. C. albicans is auxotrophic for biotin and this biotin auxotrophy was fulfilled by biotin, desthiobiotin, or KAPA. However, biotin auxotrophy is not temperature dependent or influenced by the presence of 5% CO2. Biotin starvation upregulated the biotin biosynthetic genes BIO2, BIO3, and BIO4 by 11-, 1500-, and 150-fold, respectively, and BIO2p is predicted to be mitochondrion-localized. Based on our findings, we suggest that biotin has two roles in the physiology of C. albicans, one as an enzymatic cofactor and another as a morphological regulator. Finally, we found no evidence supporting prior claims that C. albicans only forms hyphae at very low biotin (0.1 nM) growth conditions. Full article
(This article belongs to the Special Issue Fungal Nutrition Assimilation Strategies and Pathogenicity)
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Review

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Open AccessReview Nutritional Requirements and Their Importance for Virulence of Pathogenic Cryptococcus Species
Microorganisms 2017, 5(4), 65; https://doi.org/10.3390/microorganisms5040065
Received: 17 August 2017 / Revised: 27 September 2017 / Accepted: 27 September 2017 / Published: 30 September 2017
Cited by 4 | PDF Full-text (313 KB) | HTML Full-text | XML Full-text
Abstract
Cryptococcus sp. are basidiomycete yeasts which can be found widely, free-living in the environment. Interactions with natural predators, such as amoebae in the soil, are thought to have promoted the development of adaptations enabling the organism to survive inside human macrophages. Infection with [...] Read more.
Cryptococcus sp. are basidiomycete yeasts which can be found widely, free-living in the environment. Interactions with natural predators, such as amoebae in the soil, are thought to have promoted the development of adaptations enabling the organism to survive inside human macrophages. Infection with Cryptococcus in humans occurs following inhalation of desiccated yeast cells or spore particles and may result in fatal meningoencephalitis. Human disease is caused almost exclusively by the Cryptococcus neoformans species complex, which predominantly infects immunocompromised patients, and the Cryptococcus gattii species complex, which is capable of infecting immunocompetent individuals. The nutritional requirements of Cryptococcus are critical for its virulence in animals. Cryptococcus has evolved a broad range of nutrient acquisition strategies, many if not most of which also appear to contribute to its virulence, enabling infection of animal hosts. In this review, we summarise the current understanding of nutritional requirements and acquisition in Cryptococcus and offer perspectives to its evolution as a significant pathogen of humans. Full article
(This article belongs to the Special Issue Fungal Nutrition Assimilation Strategies and Pathogenicity)
Open AccessReview Phosphate Acquisition and Virulence in Human Fungal Pathogens
Microorganisms 2017, 5(3), 48; https://doi.org/10.3390/microorganisms5030048
Received: 20 July 2017 / Revised: 15 August 2017 / Accepted: 16 August 2017 / Published: 22 August 2017
Cited by 6 | PDF Full-text (1087 KB) | HTML Full-text | XML Full-text
Abstract
The ability of pathogenic fungi to acquire essential macro and micronutrients during infection is a well-established virulence trait. Recent studies in the major human fungal pathogens Candida albicans and Cryptococcus neoformans have revealed that acquisition of the essential macronutrient, phosphate, is essential for [...] Read more.
The ability of pathogenic fungi to acquire essential macro and micronutrients during infection is a well-established virulence trait. Recent studies in the major human fungal pathogens Candida albicans and Cryptococcus neoformans have revealed that acquisition of the essential macronutrient, phosphate, is essential for virulence. The phosphate sensing and acquisition pathway in fungi, known as the PHO pathway, has been extensively characterized in the model yeast Saccharomyces cerevisiae. In this review, we highlight recent advances in phosphate sensing and signaling mechanisms, and use the S. cerevisiae PHO pathway as a platform from which to compare the phosphate acquisition and storage strategies employed by several human pathogenic fungi. We also explore the multi-layered roles of phosphate acquisition in promoting fungal stress resistance to pH, cationic, and oxidative stresses, and describe emerging roles for the phosphate storage molecule polyphosphate (polyP). Finally, we summarize the recent studies supporting the necessity of phosphate acquisition in mediating the virulence of human fungal pathogens, highlighting the concept that this requirement is intimately linked to promoting resistance to host-imposed stresses. Full article
(This article belongs to the Special Issue Fungal Nutrition Assimilation Strategies and Pathogenicity)
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Open AccessReview Purine Acquisition and Synthesis by Human Fungal Pathogens
Microorganisms 2017, 5(2), 33; https://doi.org/10.3390/microorganisms5020033
Received: 31 May 2017 / Revised: 6 June 2017 / Accepted: 6 June 2017 / Published: 8 June 2017
Cited by 7 | PDF Full-text (769 KB) | HTML Full-text | XML Full-text
Abstract
While members of the Kingdom Fungi are found across many of the world’s most hostile environments, only a limited number of species can thrive within the human host. The causative agents of the most common invasive fungal infections are Candida albicans, Aspergillus [...] Read more.
While members of the Kingdom Fungi are found across many of the world’s most hostile environments, only a limited number of species can thrive within the human host. The causative agents of the most common invasive fungal infections are Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. During the infection process, these fungi must not only combat the host immune system while adapting to dramatic changes in temperature and pH, but also acquire sufficient nutrients to enable growth and dissemination in the host. One class of nutrients required by fungi, which is found in varying concentrations in their environmental niches and the human host, is the purines. These nitrogen-containing heterocycles are one of the most abundant organic molecules in nature and are required for roles as diverse as signal transduction, energy metabolism and DNA synthesis. The most common life-threatening fungal pathogens can degrade, salvage and synthesize de novo purines through a number of enzymatic steps that are conserved. While these enable them to adapt to the changing purine availability in the environment, only de novo purine biosynthesis is essential during infection and therefore an attractive antimycotic target. Full article
(This article belongs to the Special Issue Fungal Nutrition Assimilation Strategies and Pathogenicity)
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