Anticipatory Stress Responses and Immune Evasion in Fungal Pathogens

Pradhan, Arnab; Ma, Qinxi; Assis, Leandro José de; Leaves, Ian; Larcombe, Daniel E.; Rondon, Alejandra V. Rodriguez; Nev, Olga A.; Brown, Alistair J. P.

doi:10.1016/j.tim.2020.09.010

Cited by 21 publications

(29 citation statements)

References 117 publications

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“…Although the overall genome PQS frequency in A. fumigatus was one of the lowest amongst the aspergilli, the average PQS frequencies in genes involved in virulence and gliotoxin synthesis, or those upregulated in response to conditions such as hypoxia, iron limitation and oxidative stress, appeared to be much higher than the average genome frequency. GO-term enrichment analysis implicated potential roles for PQS-containing genes in functions associated with virulence in pathogenic fungi such as zinc-ion binding [ 66 ], riboflavin and tryptophan biosynthesis [ 67 ], melanin [ 68 ] and secondary metabolite synthesis [ 69 ], metallopeptidase activity [ 70 ], and the response to environmental stimuli [ 71 ]. Moreover, PQS were predominantly found in genes associated with fungal metabolism.…”

Section: Discussionmentioning

confidence: 99%

Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?

et al. 2021

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Fungal infections cause >1 million deaths annually and the emergence of antifungal resistance has prompted the exploration for novel antifungal targets. Quadruplexes are four-stranded nucleic acid secondary structures, which can regulate processes such as transcription, translation, replication and recombination. They are also found in genes linked to virulence in microbes, and ligands that bind to quadruplexes can eliminate drug-resistant pathogens. Using a computational approach, we quantified putative quadruplex-forming sequences (PQS) in 1359 genomes across the fungal kingdom and explored their presence in genes related to virulence, drug resistance and biological processes associated with pathogenicity in Aspergillus fumigatus. Here we present the largest analysis of PQS in fungi and identify significant heterogeneity of these sequences throughout phyla, genera and species. PQS were genetically conserved in Aspergillus spp. and frequently pathogenic species appeared to contain fewer PQS than their lesser/non-pathogenic counterparts. GO-term analysis identified that PQS-containing genes were involved in processes linked with virulence such as zinc ion binding, the biosynthesis of secondary metabolites and regulation of transcription in A. fumigatus. Although the genome frequency of PQS was lower in A. fumigatus, PQS could be found enriched in genes involved in virulence, and genes upregulated during germination and hypoxia. Moreover, PQS were found in genes involved in drug resistance. Quadruplexes could have important roles within fungal biology and virulence, but their roles require further elucidation.

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Section: Discussionmentioning

confidence: 99%

Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?

et al. 2021

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“…Burkholderia , in response to high cell density, anticipates stationary phase stress and triggers anticipatory response ( Goo et al, 2012 ). Fungal pathogens have been shown to elicit anticipatory response for protection against attack from the immune system of the host ( Pradhan et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Experimental Evolution of Anticipatory Regulation in Escherichia coli

et al. 2022

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Environmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby triggering response to a yet to appear cue. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution of Escherichia coli in alternating environments of rhamnose and paraquat for ∼850 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Genome sequencing reveals that this anticipatory regulation is encoded via mutations in global regulators. Overall, our study contributes to understanding of how environment shapes the topology of regulatory networks in an organism.

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“…Overall, the modulation in morphogenesis enables this pathogen to survive and set its pathogenicity under different growth and environmental conditions [21]. The ability of C. albicans to reversibly switch between different morphologic forms is a crucial virulence determinant, as the different candidal morphologic forms behave differently in pathogenicity processes and immune interactions, due to structural and growth behavioral differences between these forms [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Candida albicans blastospores and hyphae respond differentially to fluconazole: additional virulence factor of germination process

Shehata

2021

Microbes and Infectious Diseases

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Anticipatory Stress Responses and Immune Evasion in Fungal Pathogens

Cited by 21 publications

References 117 publications

Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?

Analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets?

Experimental Evolution of Anticipatory Regulation in Escherichia coli

Candida albicans blastospores and hyphae respond differentially to fluconazole: additional virulence factor of germination process

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