A unique aspartyl protease gene expansion in <i>Talaromyces marneffei</i> plays a role in growth inside host phagocytes

Payne, Michael; Weerasinghe, Harshini; Tedja, Irma; Andrianopoulos, Alex

doi:10.1080/21505594.2019.1593776

Cited by 11 publications

(13 citation statements)

References 46 publications

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“…Reproduction in host immune cell phagocytes is an excellent survival strategy for this facultative intracellular pathogen to evade adaptive immune response. T.marneffei has a series of self protection mechanism against lethal effect from macrophage, such as MAPK signal cascade, melanin molecule, heat shock protein, binary conversion, laccase, cytochrome P450, modi cation of gene expression and so on which cause macrophages fragmentation, and the spread of infection [2][3][4] . With T.marneffei infection macrophage pattern recognition receptors and risk-related molecular pattern receptors are activated, secreting a variety of anti-in ammatory factors, and up-regulating CD86 on macrophages which is bene cial for host elimination of T.marneffei.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Talaromyces Marneffei Infection on CD86 Expression in THP-1 Cells

Yang

Lin

Chen

et al. 2020

Preprint

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Background: Talaromyces Marneffei (T.marneffei) is an destructive opportunistic dimorphic fungal which can cause lethiferous Talaromycosis, but the clearance of T.marneffei mainly depends on the innate immune response. Objectives: To investigate the effect of T.marneffei on CD86 expression in THP-1 cells after infection and discuss the potential mechanisms. Methods: Western blot and immunoelectron microscopy were used to detect the CD86 expression on T.marneffei cultured on BHI medium at 37℃. Western blot、enzyme-linked immunoassay and immunofluorescence were used to detect the change of CD86 expression on macrophages incubating with T.marneffei. Enzyme-linked immunoassay was used to detect the content of CD86 in supernatant in the co-culture system. Immunohistochemistry and immunoelectron microscopy were used to detect the expression of CD86 on T.marneffei incubating with macrophages. Results: T.marneffei didn’t express CD86 when cultured separately at 37℃ detected by western blot and immunoelectron microscopy, but it did express CD86 when incubated with macrophages detected by immunohistochemistry and immunoelectron microscopy. The CD86 expression of macrophages significantly decreased at 72 hours when infected with T.marneffei while the content of CD86 in supernatant significantly increased at 72 hours compared with the control group which were detected by western blot, enzyme-linked immunoassay and immunofluorescence. Conclusion: 1.After T.marneffei infection，CD86 expression on THP-1 decreased，and with the progression of infection, insufficient polarization of M1 macrophages gradually appeared；2.T.marneffei may adsorb or uptake CD86 in supernatant produced by macrophages during the contact with THP-1 cells, thus leading to the consumption of CD86 in macrophages.

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Section: Introductionmentioning

confidence: 99%

The Effect of Talaromyces Marneffei Infection on CD86 Expression in THP-1 Cells

Yang

Lin

Chen

et al. 2020

Preprint

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“…Acid proteases have been related to the morphological modulation of fungi, such as Ustilago maydis , Talaromyces marneffei , and Candida albicans [ 45 , 46 , 47 ]. Then, we examined the effects of aspartic protease inhibition in the mycelium-to-yeast (M→Y) dimorphic transition in P. brasiliensis .…”

Section: Resultsmentioning

confidence: 99%

“…However, it is possible to observe a specific regulation for PbSAP and PbSAP2 in the absence of both nutrients compared to PbYAP1 and PbYAP2 , which preferentially demonstrated an increase in their gene expression in the presence of the nitrogen source. Recently, Talaromyces marneffei aspartyl protease gene deletion has been shown to affect intracellular growth and reduce pathogenicity in fungus [ 46 ]. However, the individual role of each aspartic protease can be defined only using genetic manipulation techniques for the deletion (knockout) of each gene and its virulence assessment.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism

Silva

Segura

Oliveira

et al. 2023

JoF

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Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. The infection begins after inhalation of the fungal propagules and their thermo-dimorphic shift to yeast form. Proteases play an important role in the host invasion process and immune modulation in many pathogenic microorganisms. Aspartyl proteases are virulence factors in many human fungal pathogens that play an important role in the host invasion process morphogenesis, cellular function, immunity, and nutrition. In the present study, we characterized the modulation of acid proteases from Paracoccidioides brasiliensis. We detected four aspartyl proteases in P. brasiliensis with high homology to aspartic protease from Saccharomyces cerevisiae Pep4. Furthermore, we demonstrated that Pepstatin A can inhibit dimorphic switching (mycelium→yeast) in P. brasiliensis. In addition, these genes were modulated during thermo-dimorphism (M→Y transition) in the presence or absence of carbon and nitrogen sources and during growth at pH 4 during 24 and 48 h. We also observed that P. brasiliensis increase the secretion of aspartic proteases when cultivated at pH 4, and these acid proteases cleave BSA, collagen, and hemoglobin. These data suggest that aspartyl proteases are modulated by environmental conditions and during fungal thermo-dimorphism. Thus, this work brings new possibilities for studying the role of aspartyl proteases in the host–pathogen relationship and P. brasiliensis biology.

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“…Organellar two-pore channels (TPCs) Belonging to the voltage-gated ion channel superfamily, [ 13 ] function as a homodimer with each subunit containing two homologous Shaker -like 6-TM repeats. [ 14 ] TPCs, are associated with various physiological processes in mammalian, such as autophagy regulation, [ 15 ] mTOR-dependent nutrient sensing, [ 16 ] lipid metabolism [ 17 ] and Ebola virus infection. Since TPCs are ubiquitously expressed in animals and plants [ 18 ] and TM is subjected to fungus, there was no TPCs in T marneffei.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of the pathogenic mechanism of talaromyces marneffei infection

Cen

Chen

Qiu³

et al. 2020

Medicine

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Background: Talaromyces marneffei (T marneffei), known as a significant pathogen in patients with AIDS in Southeast Asia, is a dimorphic fungus, which can cause deadly systematic infection in immunocompromised hosts. What is more, the dimorphic phase transition has been reported as a conspicuous process linked with virulence. Interestingly, the yeast form was found in infected individuals, representing the pathogenic phase. However, few researches were found to study the mechanism of dimorphic transition. Thus, a diverse insight into the dimorphic switch mechanism, is urgently needed and we are the first one to research the mechanism of dimorphism. Methods: Firstly, we investigated the microarray of T. marneffei in the Gene Expression Omnibus database (GEO) for differentially expressed genes (DEGs). Then Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 was employed to analyze the underlying enrichment and pathway in biological process of DEGs. Meanwhile, protein-protein interaction (PPI) network was constructed using STRING database. On the strength of the theory that similar amino acid sequences share similar structures, which play a decisive role on the function of protein, three dimensional structures of hub-genes were predicted to further investigate the likely function of hub-genes. Results: GSE51109 was elected as the eligible series for the purpose of our research, including GSM1238923 (GSM23), GSM1238924 (GSM24), and GSM1238925 (GSM25). PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were the most remarkable genes in all of the three PPI networks, thus, were viewed as hub-genes. With regard to the three-dimensional construction, except that there was no significant prediction structure of PMAA_092900 with the criterion seq identify > 30%, GMQE: 0-1, QMEAN4: -4-0, the parallel templates for four structures were Crystal structure of Saccharomyces cerevesiae mitochondrial NADP(+)-dependent isocitrate dehydrogenase in complex with isocitrate, Organellar two-pore channels (TPCs), Yeast Isocitrate Dehydrogenase (Apo Form) and Crystal Structure Of ATP-Dependent Phosphoenolpyruvate Carboxykinase From Thermus thermophilus HB8 in order. Conclusion: The dimorphic transition of T. marneffei was viewed as a pathogenic factor and DEGs were observed. In-depth study of the function and pathway of DEGs revealed that PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were most likely acting as the hub-genes and were likely taking effect through regulating energy metabolism.

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A unique aspartyl protease gene expansion in Talaromyces marneffei plays a role in growth inside host phagocytes

Cited by 11 publications

References 46 publications

The Effect of Talaromyces Marneffei Infection on CD86 Expression in THP-1 Cells

The Effect of Talaromyces Marneffei Infection on CD86 Expression in THP-1 Cells

Characterization of Aspartic Proteases from Paracoccidioides brasiliensis and Their Role in Fungal Thermo-Dimorphism

Bioinformatic analysis of the pathogenic mechanism of talaromyces marneffei infection

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