The host-infecting fungal transcriptome

Cairns, Timothy C.; Minuzzi, Florencia; Bignell, Elaine

doi:10.1111/j.1574-6968.2010.01961.x

Cited by 42 publications

(28 citation statements)

References 43 publications

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“…Alternatively, clustering of these genes at subtelomeric loci may be a strategy for coordinated regulation of virulence gene expression. Movement of these clusters into subtelomeric regions would place them under the regulatory control of LaeA, a factor that regulates gene expression through chromatin remodeling (9). Microarray data support the idea that clustering facilitates the coordinated epigenetic regulation of virulence gene expression, as ϳ30% of clustered genes are induced during initiation of invasive aspergillosis in a mouse infection model (38).…”

Section: Evolution Of Virulence-associated Genes In Pathogenic Fungimentioning

confidence: 65%

Comparative Genomics and the Evolution of Pathogenicity in Human Pathogenic Fungi

2011

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Because most fungi have evolved to be free-living in the environment and because the infections they cause are usually opportunistic in nature, it is often difficult to identify specific traits that contribute to fungal pathogenesis. In recent years, there has been a surge in the number of sequenced genomes of human fungal pathogens, and comparison of these sequences has proved to be an excellent resource for exploring commonalities and differences in how these species interact with their hosts. In order to survive in the human body, fungi must be able to adapt to new nutrient sources and environmental stresses. Therefore, genes involved in carbohydrate and amino acid metabolism and transport and genes encoding secondary metabolites tend to be overrepresented in pathogenic species (e.g., Aspergillus fumigatus). However, it is clear that human commensal yeast species such as Candida albicans have also evolved a range of specific factors that facilitate direct interaction with host tissues. The evolution of virulence across the human pathogenic fungi has occurred largely through very similar mechanisms. One of the most important mechanisms is gene duplication and the expansion of gene families, particularly in subtelomeric regions. Unlike the case for prokaryotic pathogens, horizontal transfer of genes between species and other genera does not seem to have played a significant role in the evolution of fungal virulence. New sequencing technologies promise the prospect of even greater numbers of genome sequences, facilitating the sequencing of multiple genomes and transcriptomes within individual species, and will undoubtedly contribute to a deeper insight into fungal pathogenesis.

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Section: Evolution Of Virulence-associated Genes In Pathogenic Fungimentioning

confidence: 65%

Comparative Genomics and the Evolution of Pathogenicity in Human Pathogenic Fungi

2011

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“…These niches differ with respect to the types and concentrations of available carbon and nitrogen sources, and with regard to micronutrient levels. Fungal pathogens respond by tuning their nutrient acquisition and assimilation mechanisms accordingly (Steen et al 2003;Lorenz et al 2004;Fan et al 2005;Fradin et al 2005;Kaur et al 2007;Thewes et al 2007;Zakikhany et al 2007;McDonagh et al 2008;Walker et al 2009;Wilson et al 2009;Cairns et al 2010;Staib et al 2010;Cheng et al 2013). In some instances, the host actively reduces the availability of essential nutrients in an attempt to limit fungal colonization.…”

Section: Discussionmentioning

confidence: 99%

“…However, transcriptional profiling studies using microarrays or serial analysis of gene expression (SAGE) in ex vivo or in vivo infection models have provided insights into the nitrogen metabolism of pathogenic fungi such as C. albicans (Fradin et al 2005;Thewes et al 2007;Zakikhany et al 2007;Walker et al 2009;Wilson et al 2009;Cheng et al 2013), C. glabrata (Kaur et al 2007), A. fumigatus (McDonagh et al 2008), C. neoformans (Fan et al 2005;Steen et al 2003), and dermatophytes (Staib et al 2010) during infection (reviewed by Cairns et al 2010). …”

Section: Nitrogen Assimilationmentioning

confidence: 99%

Metabolism in Fungal Pathogenesis

Ene¹,

Brunke²,

Brown³

et al. 2014

Cold Spring Harbor Perspectives in Medicine

107

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Fungal pathogens must assimilate local nutrients to establish an infection in their mammalian host. We focus on carbon, nitrogen, and micronutrient assimilation mechanisms, discussing how these influence host -fungus interactions during infection. We highlight several emerging trends based on the available data. First, the perturbation of carbon, nitrogen, or micronutrient assimilation attenuates fungal pathogenicity. Second, the contrasting evolutionary pressures exerted on facultative versus obligatory pathogens have led to contemporary pathogenic fungal species that display differing degrees of metabolic flexibility. The evolutionarily ancient metabolic pathways are conserved in most fungal pathogen, but interesting gaps exist in some species (e.g., Candida glabrata). Third, metabolic flexibility is generally essential for fungal pathogenicity, and in particular, for the adaptation to contrasting host microenvironments such as the gastrointestinal tract, mucosal surfaces, bloodstream, and internal organs. Fourth, this metabolic flexibility relies on complex regulatory networks, some of which are conserved across lineages, whereas others have undergone significant evolutionary rewiring. Fifth, metabolic adaptation affects fungal susceptibility to antifungal drugs and also presents exciting opportunities for the development of novel therapies. N utrient assimilation is a central and fundamental prerequisite for the growth and survival of all living organisms. Pathogenic fungi inhabit dynamic and contrasting niches and must display rapid and effective adaptation to changes in nutrient availability in these microenvironments. To achieve this, they regulate specific nutrient uptake mechanisms and modulate their metabolism, displaying an impressive degree of metabolic flexibility. This metabolic flexibility, which enhances the fitness of the fungus, is often as essential for pathogenicity as virulence factors, thereby representing an attractive target for potential therapeutic intervention.The major fungal pathogens of humans have evolved in a polyphyletic manner (i.e., pathogenicity has emerged independently in different

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“…However, in those studies, the authors compared fungal growth in vivo (during infection) vs. in vitro (on culture media) [21,22]. Therefore, the interpretation of these results and the subsequent conclusions have to be taken with caution, since transcriptomic studies depend on the experimental design, the time points studied and the type of reference sample used [28]. Our study was designed so that the first day of infection was used as reference, this was to avoid comparisons with in vitro conditions which may have led to differences connected to the culture conditions but not to the infectious process.…”

Section: Discussionmentioning

confidence: 99%

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus

et al. 2018

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Virulence mechanisms of the pathogenic fungus Aspergillus fumigatus are multifactorial and depend on the immune state of the host, but little is known about the fungal mechanism that develops during the process of lung invasion. In this study, microarray technology was combined with a histopathology evaluation of infected lungs so that the invasion strategy followed by the fungus could be described. To achieve this, an intranasal mice infection was performed to extract daily fungal samples from the infected lungs over four days post-infection. The pathological study revealed a heavy fungal progression throughout the lung, reaching the blood vessels on the third day after exposure and causing tissue necrosis. One percent of the fungal genome followed a differential expression pattern during this process. Strikingly, most of the genes of the intertwined fumagillin/pseurotin biosynthetic gene cluster were upregulated as were genes encoding lytic enzymes such as lipases, proteases (DppIV, DppV, Asp f 1 or Asp f 5) and chitinase (chiB1) as well as three genes related with pyomelanin biosynthesis process. Furthermore, we demonstrate that fumagillin is produced in an in vitro pneumocyte cell line infection model and that loss of fumagillin synthesis reduces epithelial cell damage. These results suggest that fumagillin contributes to tissue damage during invasive aspergillosis. Therefore, it is probable that A. fumigatus progresses through the lungs via the production of the mycotoxin fumagillin combined with the secretion of lytic enzymes that allow fungal growth, angioinvasion and the disruption of the lung parenchymal structure.

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The host-infecting fungal transcriptome

Cited by 42 publications

References 43 publications

Comparative Genomics and the Evolution of Pathogenicity in Human Pathogenic Fungi

Comparative Genomics and the Evolution of Pathogenicity in Human Pathogenic Fungi

Metabolism in Fungal Pathogenesis

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus

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