Proteomic analysis of <i>Aspergillus fumigatus</i> – clinical implications

Moloney, Nicola M.; Owens, Rebecca A.; Doyle, Seán

doi:10.1080/14789450.2016.1203783

Cited by 12 publications

(7 citation statements)

References 130 publications

(201 reference statements)

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“…Annotation is complicated in that A. fumigatus is rich in protein families which have different functions in spite of similar sequences and in that the redundancy of certain gene families requires multiple deletions to assess a relevant phenotype (e.g., chitin synthase gene family) (165,166). Transcriptome (167)(168)(169)(170) and proteome (171)(172)(173)(174)(175) databases are becoming available and will be used to compare omics data obtained under different conditions. It should be noted that the genetic background of the parental strain is important and may complicate the omics studies, since parental fungal strains may differ in virulence (176).…”

Section: Tools and Strategies To Study The Pathobiology Of A Fumigatmentioning

confidence: 99%

Aspergillus fumigatus and Aspergillosis in 2019

2019

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SUMMARY Aspergillus fumigatus is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of A. fumigatus; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against Aspergillus in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of A. fumigatus.

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Section: Tools and Strategies To Study The Pathobiology Of A Fumigatmentioning

confidence: 99%

Aspergillus fumigatus and Aspergillosis in 2019

2019

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“…Enolase (Aspf 22) has been reported an allergen which stimulates a strong IFNγ immune response in humans and its homolog in C. albicans showed partial protection as a vaccine candidate (Denikus et al 2005 ; Chaudhary et al 2010 ). Presence of enolase (involved in energy metabolism) in hyphae of Aspergilli suggests that this enzyme may facilitate tissue invasion in the host (Denikus et al 2005 ; Moloney et al 2016 ; Shankar et al 2018 ). In A. fumigatus , enolase was abundantly expressed under the influence of antifungal drug suggesting energy metabolism is vital to overcoming the drug stress.…”

Section: Proteomic Approach To Characterise the Antifungal Response Imentioning

confidence: 99%

Resistance mechanism and proteins in Aspergillus species against antifungal agents

2019

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Aspergillus species contain pathogenic and opportunistic fungal pathogens which have the potential to cause mycosis (invasive aspergillosis) in humans. The existing antifungal drugs have limitation largely due to the development of drug-resistant isolates. To gain insight into the mechanism of action and antifungal drug resistance in Aspergillus species including biofilm formation, we have reviewed protein data of Aspergillus species during interaction with antifungals drugs (polynes, azoles and echinocandin) and phytochemicals (artemisinin, coumarin and quercetin). Our analyses provided a list of Aspergillus proteins (72 proteins) that were abundant during interaction with different antifungal agents. On the other hand, there are 26 proteins, expression level of which is affected by more than two antifungal agents, suggesting the more general response to the stress induced by the antifungal agents. Our analysis showed enzymes from cell wall remodelling, oxidative stress response and energy metabolism are the responsible factors for providing resistance against antifungal drugs in Aspergillus species and could be explored further in clinical isolates. Also, these findings have clinical importance since the effect of drug targeting different proteins can be potentiated by combination therapy. We have also discussed the opportunities ahead to study the functional role of proteins from environmental and clinical isolates of Aspergillus during its interaction with the antifungal drugs. Abbreviations IPA: invasive pulmonary aspergillosis; IA: invasive aspergillosis; AmB: Amphotericin B; CAS: Caspofungin; VRC: Voriconazole; ITC: Itraconazole; POS: Posaconazole; ART: Artemisinin; QRT: Quercetin; CMR: Coumarin; MIC: minimal inhibitory concentration

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“…Previous studies on A. fumigatus using 2-DE and MALDI-TOF showed higher expression of protein that function in metabolism, protein biosynthesis, transport, and translation initiation factors in germinating conidia as compared to hyphae (Vödisch et al, 2009 ; Kubitschek-Barreira et al, 2013 ). Proteins from primary metabolism such as enolase/Aspf22 and glyceraldehyde 3-phosphate dehydrogenase were observed on hyphal surface suggesting that these proteins act as adhesion molecules against host (Denikus et al, 2005 ; Moloney et al, 2016 ). Using 2D-DIGE approach, it has been observed that proteins involved in secondary biosynthetic pathways and proteins biosynthesis were over expressed in germinating conidia, while in hyphae, most abundant proteins expressed were from metabolic processes (Kubitschek-Barreira et al, 2013 ).…”

Section: Determinants To Exit Conidial Dormancymentioning

confidence: 99%

Molecular Insights Into Development and Virulence Determinants of Aspergilli: A Proteomic Perspective

Shankar

Tiwari

Shishodia

et al. 2018

Front. Cell. Infect. Microbiol.

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Aspergillus species are the major cause of health concern worldwide in immunocompromised individuals. Opportunistic Aspergilli cause invasive to allergic aspergillosis, whereas non-infectious Aspergilli have contributed to understand the biology of eukaryotic organisms and serve as a model organism. Morphotypes of Aspergilli such as conidia or mycelia/hyphae helped them to survive in favorable or unfavorable environmental conditions. These morphotypes contribute to virulence, pathogenicity and invasion into hosts by excreting proteins, enzymes or toxins. Morphological transition of Aspergillus species has been a critical step to infect host or to colonize on food products. Thus, we reviewed proteins from Aspergilli to understand the biological processes, biochemical, and cellular pathways that are involved in transition and morphogenesis. We majorly analyzed proteomic studies on A. fumigatus, A. flavus, A. terreus, and A. niger to gain insight into mechanisms involved in the transition from conidia to mycelia along with the role of secondary metabolites. Proteome analysis of morphotypes of Aspergilli provided information on key biological pathways required to exit conidial dormancy, consortia of virulent factors and mycotoxins during the transition. The application of proteomic approaches has uncovered the biological processes during development as well as intermediates of secondary metabolite biosynthesis pathway. We listed key proteins/ enzymes or toxins at different morphological types of Aspergillus that could be applicable in discovery of novel therapeutic targets or metabolite based diagnostic markers.

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Proteomic analysis of Aspergillus fumigatus – clinical implications

Cited by 12 publications

References 130 publications

Aspergillus fumigatus and Aspergillosis in 2019

Aspergillus fumigatus and Aspergillosis in 2019

Resistance mechanism and proteins in Aspergillus species against antifungal agents

Molecular Insights Into Development and Virulence Determinants of Aspergilli: A Proteomic Perspective

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