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Aspergillosis is a fungal infection caused by various species of Aspergillus, most notably A. fumigatus. This fungus causes a spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis. The clinical manifestations and severity of aspergillosis can vary depending on individual immune status and the specific species of Aspergillus involved. The recognition of Aspergillus involves pathogen-associated molecular patterns (PAMPs) such as glucan, galactomannan, mannose, and conidial surface proteins. These are recognized by the pathogen recognition receptors present on immune cells such as Toll-like receptors (TLR-1,2,3,4, etc.) and C-type lectins (Dectin-1 and Dectin-2). We discuss the roles of cytokines and pathogen recognition in aspergillosis from both the perspective of human and experimental infection. Several cytokines and chemokines have been implicated in the immune response to Aspergillus infection, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), CCR4, CCR17, and other interleukins. For example, allergic bronchopulmonary aspergillosis (ABPA) is characterized by Th2 and Th9 cell-type immunity and involves interleukin (IL)-4, IL-5, IL-13, and IL-10. In contrast, it has been observed that invasive aspergillosis involves Th1 and Th17 cell-type immunity via IFN-γ, IL-1, IL-6, and IL-17. These cytokines activate various immune cells and stimulate the production of other immune molecules, such as antimicrobial peptides and reactive oxygen species, which aid in the clearance of the fungal pathogen. Moreover, they help to initiate and coordinate the immune response, recruit immune cells to the site of infection, and promote clearance of the fungus. Insight into the host response from both human and animal studies may aid in understanding the immune response in aspergillosis, possibly leading to harnessing the power of cytokines or cytokine (receptor) antagonists and transforming them into precise immunotherapeutic strategies. This could advance personalized medicine. [ABSTRACT FROM AUTHOR]

Aspergillus niger is a ubiquitous organism that impacts clinical settings and the biotechnology industries. To gain insight into the germination of conidia in A. niger, a gel-free protein profile could be a platform to illustrate critical proteins and their involvement in biochemical pathways during germination. A clinical isolate of A. niger (NCCPF 790032) cultured on Sabouraud dextrose showed more than 90% conidia germination at the 7 h time point. To profile proteins, protein extraction and estimation were followed by nLC-qTOF mass spectrometer analysis. Using the UniProt database, Protein Lynx Global Service (PLGS 3.0.2) software analyses showed 883 proteins across Aspergillus spp., including 108 proteins to A. niger. Orthologues of A. niger's protein were observed in A. nidulans, A. fumigatus, A. clavatus, A. oryzae, A. fischeri, A. terreus, A. flavus, A. parasiticus, A. kawachii, A. aculaetus, A. awamori, A. ficuum, A. tubingensis, A. versicolor, Augochlora phoenicis, and Anexaireta variicolor. Proteins categorized based on Gene Ontology (GO) (biological process, molecular function, and cellular component) clustered primarily to GO terms belonging to cell wall biogenesis, energy, carbohydrate, amino acid, protein metabolism synthesis, among the others. The expression of serine-threonine protein kinases during the germinating conidia of A. niger involved in MAPK-mediated signaling was observed. Expression of tyrosinase in A. niger favored conidial pigmentation via the DOPA-melanin biosynthesis pathway. Overall, the identity of proteins showed that these proteins belong to organelle biogenesis (ribosome, mitochondria) and metabolism of macromolecules (protein, carbohydrate, and nucleic acids) during the germination of A. niger conidia. The data could be helpful in comparative proteomics relevant to pathogenic fungi or to understand the biology of Aspergillus spp. [ABSTRACT FROM AUTHOR]

exploits diverse mechanisms to survive during exposure to antifungal agents including morphogenesis. Germination of dormant conidia involves cascades of reactions integrated into the signalling pathway. This study documents the effect of phytochemical-quercetin on A. flavus during germination of conidia using scanning electron microscopy (SEM). Significant inhibition of conidial swelling of A. flavus in comparison to control was observed at 4 and 7 h Quantitative real-time PCR for genes from calcium signalling pathway and heat-shock proteins family showed up-regulation of heat shock (Hsp70 and Hsp90) and calcium signalling pathway genes (calcium-transporting ATPase and calmodulin) in response to quercetin at initial 4 h in comparison to control sample whereas up-regulation of Hsp70, calcineurin and transcription factor Crz1, were observed in both the treated samples. Gene encoding for calcium-kinase, cAMP, Rho-gdp, Plc and Pkc showed a constitutively higher level of expression in quercetin-treated sample in comparison to control at both time points. These data showed a clear response from genes encoding calcineurin-Crz1 signalling pathways and may find its application in the screening of antifungal agents. Hsp: Hear shock protein; MIC: Minimum Inhibitory Concentration; SEM: Scanning Electron Microscopy; qRT-PCR: Quantitative Real-Time Polymerase Chain Reaction [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]