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Jianquan Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Talaromyces Marneffei and nontuberculous mycobacteria co infection in hiv negative patients
    Scientific Reports, 2021
    Co-Authors: Wen Zeng, Ye Qiu, Hui Zhang, Mianluan Pan, Jie Huang, Jiemei Cen, Xuejiao Sun, Jianquan Zhang
    Abstract:

    To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces Marneffei (TM) co-infections in HIV-negative patients. A multicenter retrospective study in 13 hospitals, and a systematic literature review were performed of original articles published in English related to TM/NTM co-infections. HIV-negative patients with TM and NTM co-infections comprised Group 1; TM-only infection Group 2; NTM-only infection Group 3; and healthy volunteers Group 4. Univariate logistic analysis was used to estimate the potential risk factors of TM/NTM co-infections. A total of 22 cases of TM and NTM co-infections were enrolled. Of these, 17 patients (77.3%) had a missed diagnosis of one of the TM or NTM pathogens. The anti-IFN-γ autoantibodies (AIGAs) titer, white blood cell (WBC), neutrophil counts (N), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), globulin, and immunoglobulin G (IgG) levels of Group 1 were higher than those of the other groups, whereas the levels of CD4+T cells was lower than those of other groups. There was a significant negative correlation between the AIGA titers and the number of CD4+T cells (P < 0.05). Factors including the ratio of the actual values to the cut-off values of AIGAs, WBC, N, HGB, CD4+T cells, IgG, IgM, IgA, serum globulin, ESR, and CRP were taken as potential risk factors for TM and NTM co-infection. Most patients with TM and NTM co-infection had a missed diagnosis of one of the TM or NTM pathogens. The levels of AIGAs, WBC, N, ESR, and CRP in TM and NTM co-infections were remarkably higher than in mono-infection. High-titer AIGAs may be a potential risk factor and susceptibility factor for co-infection of TM and NTM in HIV-negative hosts.

  • Talaromyces Marneffei and burkholderia cepacia co infection in a hiv uninfected patient with anti interferon γ autoantibodies
    Infection and Drug Resistance, 2021
    Co-Authors: Wen Zeng, Ye Qiu, Mengxin Tang, Hui Zhang, Mianluan Pan, Shudan Tang, Jianquan Zhang
    Abstract:

    A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces Marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces Marneffei and Burkholderia cepacia infection. The patient's lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections.

  • bioinformatic analysis of the pathogenic mechanism of Talaromyces Marneffei infection
    Medicine, 2020
    Co-Authors: Jiemei Cen, Wen Zeng, Ye Qiu, Jiarui Chen, Jianquan Zhang
    Abstract:

    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.

  • Talaromyces Marneffei infection in systemic lupus erythematosus patients report of two cases and review of the literature
    Infection and Drug Resistance, 2020
    Co-Authors: Jingshan Wei, Wen Zeng, Ye Qiu, Mianluan Pan, Jianquan Zhang
    Abstract:

    Purpose Talaromyces Marneffei is a highly invasive fungus, causing fatal mycosis in patients with or without HIV in Southeast and Eastern Asia. However, its presence in patients with systemic lupus erythematosus is rarely reported. Methods We reported two SLE patients infected by T. Marneffei and reviewed other patients reported in the English literature. All cases were pooled for analysis. Results Eleven patients with SLE infected with T. Marneffei infection were identified, including the two presented here. Three were male and eight were female; all were HIV negative. All the patients, except two where data were missing, had received immunosuppressants before T. Marneffei infection. The main clinical features included fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Five patients were misdiagnosed as having SLE exacerbation. T. Marneffei was detected via culture or histopathologic analysis, with the fungus most commonly found in the blood. Seven of the 11 patients were successfully treated by timely antifungal therapy with concomitant SLE control, while four patients who did not receive antifungal therapy died. Conclusion T. Marneffei infection should be excluded when SLE patients, especially if on long-term immunosuppressants, present with fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Controlling the lupus and timely antifungal treatment can improve the outcomes of SLE patients with T. Marneffei infection.

  • disseminated Talaromyces Marneffei infection presenting as multiple intestinal perforations and diffuse hepatic granulomatous inflammation in an infant with stat3 mutation a case report
    BMC Infectious Diseases, 2020
    Co-Authors: Mianluan Pan, Wen Zeng, Ye Qiu, Shudan Tang, Xuan Wei, Jianquan Zhang
    Abstract:

    Talaromyces Marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis Marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. Marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation. We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. Marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents’ revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D). In T. Marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.

Ye Qiu - One of the best experts on this subject based on the ideXlab platform.

  • Talaromyces Marneffei and nontuberculous mycobacteria co infection in hiv negative patients
    Scientific Reports, 2021
    Co-Authors: Wen Zeng, Ye Qiu, Hui Zhang, Mianluan Pan, Jie Huang, Jiemei Cen, Xuejiao Sun, Jianquan Zhang
    Abstract:

    To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces Marneffei (TM) co-infections in HIV-negative patients. A multicenter retrospective study in 13 hospitals, and a systematic literature review were performed of original articles published in English related to TM/NTM co-infections. HIV-negative patients with TM and NTM co-infections comprised Group 1; TM-only infection Group 2; NTM-only infection Group 3; and healthy volunteers Group 4. Univariate logistic analysis was used to estimate the potential risk factors of TM/NTM co-infections. A total of 22 cases of TM and NTM co-infections were enrolled. Of these, 17 patients (77.3%) had a missed diagnosis of one of the TM or NTM pathogens. The anti-IFN-γ autoantibodies (AIGAs) titer, white blood cell (WBC), neutrophil counts (N), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), globulin, and immunoglobulin G (IgG) levels of Group 1 were higher than those of the other groups, whereas the levels of CD4+T cells was lower than those of other groups. There was a significant negative correlation between the AIGA titers and the number of CD4+T cells (P < 0.05). Factors including the ratio of the actual values to the cut-off values of AIGAs, WBC, N, HGB, CD4+T cells, IgG, IgM, IgA, serum globulin, ESR, and CRP were taken as potential risk factors for TM and NTM co-infection. Most patients with TM and NTM co-infection had a missed diagnosis of one of the TM or NTM pathogens. The levels of AIGAs, WBC, N, ESR, and CRP in TM and NTM co-infections were remarkably higher than in mono-infection. High-titer AIGAs may be a potential risk factor and susceptibility factor for co-infection of TM and NTM in HIV-negative hosts.

  • Talaromyces Marneffei and burkholderia cepacia co infection in a hiv uninfected patient with anti interferon γ autoantibodies
    Infection and Drug Resistance, 2021
    Co-Authors: Wen Zeng, Ye Qiu, Mengxin Tang, Hui Zhang, Mianluan Pan, Shudan Tang, Jianquan Zhang
    Abstract:

    A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces Marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces Marneffei and Burkholderia cepacia infection. The patient's lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections.

  • Serum Sphingolipids Aiding the Diagnosis of Adult HIV-Negative Patients with Talaromyces Marneffei Infection
    'Frontiers Media SA', 2021
    Co-Authors: Lee-fong Yau, Ye Qiu, Yang-qing Zhan, Wai-him Chan, Zhao-ming Chen, Ye Lin
    Abstract:

    Increasing attention has been directed to Talaromyces Marneffei (T. Marneffei) infection in HIV-negative patients due to its high mortality rate. However, nonspecific symptoms and biological characteristics similar to those of other common pathogenic fungi complicate the rapid and accurate diagnosis of T. Marneffei infection. Sphingolipids (SPLs) are bioactive lipids involved in the regulation of various physiological and pathological processes and have been identified as serum biomarkers for several diseases. This study employed a sphingolipidomic approach established in our previous work to explore the use of serum SPLs in the diagnosis of HIV-negative patients with T. Marneffei infection. Additional clinical cohorts of patients infected with other microorganisms were also recruited. We found that sphinganine (Sa) (d16:0) exhibited obvious depletion after infection; moreover, its level in patients with T. Marneffei infection was significantly lower than that in patients infected with other microorganisms. Therefore, Sa (d16:0) was considered a specific diagnostic biomarker for T. Marneffei infection, and 302.71 nM was selected as the optimal cutoff value with a diagnostic sensitivity of 87.5% and specificity of 100%. These results suggested that determination of serum Sa (d16:0) levels can be used as a new alternative tool for the rapid diagnosis of T. Marneffei infection in HIV-negative patients

  • Clinical findings of Talaromyces Marneffei infection among patients with anti-interferon-γ immunodeficiency: a prospective cohort study
    'Springer Science and Business Media LLC', 2021
    Co-Authors: Zhao-ming Chen, Ye Qiu, Yang-qing Zhan, Wei-jie Guan, Zi-ying Lei, Hua Zhou, Sheng Lin, Xinni Wang
    Abstract:

    Abstract Background Talaromyces Marneffei (T. Marneffei) infection has been associated with adult-onset immunodeficiency due to anti-IFN-γ autoantibodies. We aimed to investigate the clinical features of non-HIV-infected patients with T. Marneffei infection in southern China. Methods Between January 2018 and September 2020, we enrolled patients with T. Marneffei infection who were HIV-negative (group TM, n = 42), including anti-IFN-γ autoantibody-positive (group TMP, n = 22) and anti-IFN-γ autoantibody-negative (group TMN, n = 20) patients and healthy controls (group HC, n = 40). Anti-IFN-γ autoantibodies were detected by ELISA. Clinical characteristics and clinical laboratory parameters were recorded. Results Compared with anti-IFN-γ autoantibody-negative patients with T. Marneffei infection, anti-IFN-γ autoantibody-positive patients did not have underlying respiratory disease; more frequently exhibited dissemination of systemic infections with severe pleural effusion; had higher WBC counts, C-reactive protein levels, erythrocyte sedimentation rates, and neutrophil and CD8+ T cell counts; had lower hemoglobin levels; and were more likely to have other intracellular pathogen infections. Most of these patients had poor outcomes despite standardized antimicrobial therapy. Conclusion T. Marneffei-infected patients with higher anti-IFN-γ autoantibody titers have more severe disease and complex clinical conditions

  • bioinformatic analysis of the pathogenic mechanism of Talaromyces Marneffei infection
    Medicine, 2020
    Co-Authors: Jiemei Cen, Wen Zeng, Ye Qiu, Jiarui Chen, Jianquan Zhang
    Abstract:

    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.

Alex Andrianopoulos - One of the best experts on this subject based on the ideXlab platform.

  • Laboratory Maintenance and Growth of Talaromyces Marneffei.
    Current protocols in microbiology, 2020
    Co-Authors: Alex Andrianopoulos
    Abstract:

    Talaromyces Marneffei is an important opportunistic human pathogen endemic to Southeast Asia. It is one of a number of pathogenic fungi that exhibits thermally controlled dimorphism. At 25°C, T. Marneffei grows in a multicellular, filamentous hyphal form that can differentiate to produce dormant spores called conidia. These conidia are the likely infectious agent. At 37°C, T. Marneffei grows as a uninucleate yeast that divides by fission. The yeast cells are the pathogenic form of this fungus. The protocols described here explain how to grow T. Marneffei in the two vegetative growth forms in vitro, grow yeast cells inside mammalian macrophages, produce conidial stocks, and store strains both short and long term. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Growth of the vegetative hyphal form on solid medium Alternate Protocol 1: Growth of the vegetative hyphal form in liquid suspension Basic Protocol 2: Growth of the vegetative yeast form on solid medium Alternate Protocol 2: Growth of the vegetative yeast form in liquid suspension Basic Protocol 3: Growth for production of dormant conidia Support Protocol: Preparation of Miracloth filter tubes Basic Protocol 4: Growth of Talaromyces Marneffei in mammalian macrophages Basic Protocol 5: Storage of Talaromyces Marneffei strains Alternate Protocol 3: Lyophilization of Talaromyces Marneffei strains.

  • A unique aspartyl protease gene expansion in Talaromyces Marneffei plays a role in growth inside host phagocytes
    2019
    Co-Authors: Michael Payne, Harshini Weerasinghe, Irma Tedja, Alex Andrianopoulos
    Abstract:

    Aspartyl proteases are a widely represented class of proteolytic enzymes found in eukaryotes and retroviruses. They have been associated with pathogenicity in a range of disease-causing microorganisms. The dimorphic human-pathogenic fungus Talaromyces Marneffei has a large expansion of these proteases identified through genomic analyses. Here we characterize the expansion of these genes (pop – paralogue of pep) and their role in T. Marneffei using computational and molecular approaches. Many of the genes in this monophyletic family show copy number variation and positive selection despite the preservation of functional regions and possible redundancy. We show that the expression profile of these genes differs and some are expressed during intracellular growth in the host. Several of these proteins have distinctive localization as well as both additive and epistatic effects on the formation of yeast cells during macrophage infections. The data suggest that this is a recently evolved aspartyl protease gene family which affects intracellular growth and contributes to the pathogenicity of T. Marneffei.

  • the novel dbl homology bar domain protein msga of Talaromyces Marneffei regulates yeast morphogenesis during growth inside host cells
    bioRxiv, 2018
    Co-Authors: Harshini Weerasinghe, Hayley E Bugeja, Alex Andrianopoulos
    Abstract:

    Abstract Microbial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37°C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces Marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. Marneffei that controls intracellular yeast morphogenesis.

  • extensive metabolic remodeling differentiates non pathogenic and pathogenic growth forms of the dimorphic pathogen Talaromyces Marneffei
    Frontiers in Cellular and Infection Microbiology, 2017
    Co-Authors: Shivani Pasricha, James I Macrae, Hwa H Chua, Jenny L Chambers, Kylie J Boyce, Malcolm J Mcconville, Alex Andrianopoulos
    Abstract:

    Fungal infections are an increasing public health problem, particularly in immunocompromised individuals. While these pathogenic fungi show polyphyletic origins with closely related non-pathogenic species, many undergo morphological transitions to produce pathogenic cell types that are associated with increased virulence. However, the characteristics of these pathogenic cells that contribute to virulence are poorly defined. Talaromyces Marneffei grows as a non-pathogenic hyphal form at 25°C but undergoes a dimorphic transition to a pathogenic yeast form at 37°C in vitro and following inhalation of asexual conidia by a host. Here we show that this transition is associated with major changes in central carbon metabolism, and that these changes are correlated with increased virulence of the yeast form. Comprehensive metabolite profiling and 13C-labeling studies showed that hyphal cells exhibited very active glycolytic metabolism and contain low levels of internal carbohydrate reserves. In contrast, yeast cells fully catabolized glucose in the mitochondrial TCA cycle, and store excess glucose in large intracellular pools of trehalose and mannitol. Inhibition of the yeast TCA cycle inhibited replication in culture and in host cells. Yeast, but not hyphae, were also able to use myo-inositol and amino acids as secondary carbon sources, which may support their survival in host macrophages. These analyses suggest that T. Marneffei yeast cells exhibit a more efficient oxidative metabolism and are capable of utilizing a diverse range of carbon sources, which contributes to their virulence in animal tissues, highlighting the importance of dimorphic switching in pathogenic yeast.

  • differentially regulated high affinity iron assimilation systems support growth of the various cell types in the dimorphic pathogen Talaromyces Marneffei
    Molecular Microbiology, 2016
    Co-Authors: Shivani Pasricha, Kylie J Boyce, Lukas Schafferer, Herbert Lindner, Hubertus Haas, Alex Andrianopoulos
    Abstract:

    Iron is a key trace element important for many biochemical processes and its availability varies with the environment. For human pathogenic fungi iron acquisition can be particularly problematical because host cells sequester free iron as part of the acute-phase response to infection. Fungi rely on high-affinity iron uptake systems, such as reductive iron assimilation (RIA) and siderophore-mediated iron uptake (non-RIA). These have been extensively studied in pathogenic fungi that exist outside of host cells, but much less is known for intracellular fungal pathogens. Talaromyces Marneffei is a dimorphic fungal pathogen endemic to Southeast Asia. In the host T. Marneffei resides within macrophages where it grows as a fission yeast. T. Marneffei has genes of both iron assimilation systems as well as a paralogue of the siderophore biosynthetic gene sidA, designated sidX. Unlike other fungi, deletion of sidA or sidX resulted in cell type-specific effects. Mutant analysis showed that T. Marneffei yeast cells also employ RIA for iron acquisition, providing an additional system in this cell type that differs substantially from hyphal cells. These data illustrate the specialized iron acquisition systems used by the different cell types of a dimorphic fungal pathogen and highlight the complexity in siderophore-biosynthetic pathways amongst fungi.

Wen Zeng - One of the best experts on this subject based on the ideXlab platform.

  • Talaromyces Marneffei and nontuberculous mycobacteria co infection in hiv negative patients
    Scientific Reports, 2021
    Co-Authors: Wen Zeng, Ye Qiu, Hui Zhang, Mianluan Pan, Jie Huang, Jiemei Cen, Xuejiao Sun, Jianquan Zhang
    Abstract:

    To describe the clinical features and the risk factors for nontuberculous mycobacteria (NTM) and Talaromyces Marneffei (TM) co-infections in HIV-negative patients. A multicenter retrospective study in 13 hospitals, and a systematic literature review were performed of original articles published in English related to TM/NTM co-infections. HIV-negative patients with TM and NTM co-infections comprised Group 1; TM-only infection Group 2; NTM-only infection Group 3; and healthy volunteers Group 4. Univariate logistic analysis was used to estimate the potential risk factors of TM/NTM co-infections. A total of 22 cases of TM and NTM co-infections were enrolled. Of these, 17 patients (77.3%) had a missed diagnosis of one of the TM or NTM pathogens. The anti-IFN-γ autoantibodies (AIGAs) titer, white blood cell (WBC), neutrophil counts (N), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), globulin, and immunoglobulin G (IgG) levels of Group 1 were higher than those of the other groups, whereas the levels of CD4+T cells was lower than those of other groups. There was a significant negative correlation between the AIGA titers and the number of CD4+T cells (P < 0.05). Factors including the ratio of the actual values to the cut-off values of AIGAs, WBC, N, HGB, CD4+T cells, IgG, IgM, IgA, serum globulin, ESR, and CRP were taken as potential risk factors for TM and NTM co-infection. Most patients with TM and NTM co-infection had a missed diagnosis of one of the TM or NTM pathogens. The levels of AIGAs, WBC, N, ESR, and CRP in TM and NTM co-infections were remarkably higher than in mono-infection. High-titer AIGAs may be a potential risk factor and susceptibility factor for co-infection of TM and NTM in HIV-negative hosts.

  • Talaromyces Marneffei and burkholderia cepacia co infection in a hiv uninfected patient with anti interferon γ autoantibodies
    Infection and Drug Resistance, 2021
    Co-Authors: Wen Zeng, Ye Qiu, Mengxin Tang, Hui Zhang, Mianluan Pan, Shudan Tang, Jianquan Zhang
    Abstract:

    A high titer of neutralizing anti-interferon-γ autoantibodies can cause immunodeficiency associated with severe or disseminated infections caused by Talaromyces Marneffei in human immunodeficiency virus-negative patients. Herein, we reported a rare case of disseminated Talaromyces Marneffei and Burkholderia cepacia infection. The patient's lungs, lymph nodes, and bronchi were involved, and he had neck abscesses and osteomyelitis. We measured the neutralizing anti-interferon-γ autoantibodies in the peripheral blood and found that the patient had a persistently high positive titer. Despite aggressive treatment, the patient developed disseminated intravascular coagulation and died. Thus, high-titer nAIGAs may be associated with multiple opportunistic, persistent and disseminated infections.

  • bioinformatic analysis of the pathogenic mechanism of Talaromyces Marneffei infection
    Medicine, 2020
    Co-Authors: Jiemei Cen, Wen Zeng, Ye Qiu, Jiarui Chen, Jianquan Zhang
    Abstract:

    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.

  • Talaromyces Marneffei infection in systemic lupus erythematosus patients report of two cases and review of the literature
    Infection and Drug Resistance, 2020
    Co-Authors: Jingshan Wei, Wen Zeng, Ye Qiu, Mianluan Pan, Jianquan Zhang
    Abstract:

    Purpose Talaromyces Marneffei is a highly invasive fungus, causing fatal mycosis in patients with or without HIV in Southeast and Eastern Asia. However, its presence in patients with systemic lupus erythematosus is rarely reported. Methods We reported two SLE patients infected by T. Marneffei and reviewed other patients reported in the English literature. All cases were pooled for analysis. Results Eleven patients with SLE infected with T. Marneffei infection were identified, including the two presented here. Three were male and eight were female; all were HIV negative. All the patients, except two where data were missing, had received immunosuppressants before T. Marneffei infection. The main clinical features included fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Five patients were misdiagnosed as having SLE exacerbation. T. Marneffei was detected via culture or histopathologic analysis, with the fungus most commonly found in the blood. Seven of the 11 patients were successfully treated by timely antifungal therapy with concomitant SLE control, while four patients who did not receive antifungal therapy died. Conclusion T. Marneffei infection should be excluded when SLE patients, especially if on long-term immunosuppressants, present with fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Controlling the lupus and timely antifungal treatment can improve the outcomes of SLE patients with T. Marneffei infection.

  • disseminated Talaromyces Marneffei infection presenting as multiple intestinal perforations and diffuse hepatic granulomatous inflammation in an infant with stat3 mutation a case report
    BMC Infectious Diseases, 2020
    Co-Authors: Mianluan Pan, Wen Zeng, Ye Qiu, Shudan Tang, Xuan Wei, Jianquan Zhang
    Abstract:

    Talaromyces Marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis Marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. Marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation. We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. Marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents’ revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D). In T. Marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.

Harshini Weerasinghe - One of the best experts on this subject based on the ideXlab platform.

  • A unique aspartyl protease gene expansion in Talaromyces Marneffei plays a role in growth inside host phagocytes
    2019
    Co-Authors: Michael Payne, Harshini Weerasinghe, Irma Tedja, Alex Andrianopoulos
    Abstract:

    Aspartyl proteases are a widely represented class of proteolytic enzymes found in eukaryotes and retroviruses. They have been associated with pathogenicity in a range of disease-causing microorganisms. The dimorphic human-pathogenic fungus Talaromyces Marneffei has a large expansion of these proteases identified through genomic analyses. Here we characterize the expansion of these genes (pop – paralogue of pep) and their role in T. Marneffei using computational and molecular approaches. Many of the genes in this monophyletic family show copy number variation and positive selection despite the preservation of functional regions and possible redundancy. We show that the expression profile of these genes differs and some are expressed during intracellular growth in the host. Several of these proteins have distinctive localization as well as both additive and epistatic effects on the formation of yeast cells during macrophage infections. The data suggest that this is a recently evolved aspartyl protease gene family which affects intracellular growth and contributes to the pathogenicity of T. Marneffei.

  • the novel dbl homology bar domain protein msga of Talaromyces Marneffei regulates yeast morphogenesis during growth inside host cells
    bioRxiv, 2018
    Co-Authors: Harshini Weerasinghe, Hayley E Bugeja, Alex Andrianopoulos
    Abstract:

    Abstract Microbial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37°C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces Marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. Marneffei that controls intracellular yeast morphogenesis.

  • macrophages protect Talaromyces Marneffei conidia from myeloperoxidase dependent neutrophil fungicidal activity during infection establishment in vivo
    PLOS Pathogens, 2018
    Co-Authors: Felix Ellett, Vahid Pazhakh, Luke Pase, Erica L Benard, Harshini Weerasinghe, Denis Azabdaftari, Sultan Alasmari
    Abstract:

    Neutrophils and macrophages provide the first line of cellular defence against pathogens once physical barriers are breached, but can play very different roles for each specific pathogen. This is particularly so for fungal pathogens, which can occupy several niches in the host. We developed an infection model of talaromycosis in zebrafish embryos with the thermally-dimorphic intracellular fungal pathogen Talaromyces Marneffei and used it to define different roles of neutrophils and macrophages in infection establishment. This system models opportunistic human infection prevalent in HIV-infected patients, as zebrafish embryos have intact innate immunity but, like HIV-infected talaromycosis patients, lack a functional adaptive immune system. Importantly, this new talaromycosis model permits thermal shifts not possible in mammalian models, which we show does not significantly impact on leukocyte migration, phagocytosis and function in an established Aspergillus fumigatus model. Furthermore, the optical transparency of zebrafish embryos facilitates imaging of leukocyte/pathogen interactions in vivo. Following parenteral inoculation, T. Marneffei conidia were phagocytosed by both neutrophils and macrophages. Within these different leukocytes, intracellular fungal form varied, indicating that triggers in the intracellular milieu can override thermal morphological determinants. As in human talaromycosis, conidia were predominantly phagocytosed by macrophages rather than neutrophils. Macrophages provided an intracellular niche that supported yeast morphology. Despite their minor role in T. Marneffei conidial phagocytosis, neutrophil numbers increased during infection from a protective CSF3-dependent granulopoietic response. By perturbing the relative abundance of neutrophils and macrophages during conidial inoculation, we demonstrate that the macrophage intracellular niche favours infection establishment by protecting conidia from a myeloperoxidase-dependent neutrophil fungicidal activity. These studies provide a new in vivo model of talaromycosis with several advantages over previous models. Our findings demonstrate that limiting T. Marneffei’s opportunity for macrophage parasitism and thereby enhancing this pathogen’s exposure to effective neutrophil fungicidal mechanisms may represent a novel host-directed therapeutic opportunity.

  • organism wide studies into pathogenicity and morphogenesis in Talaromyces Marneffei
    Future Microbiology, 2016
    Co-Authors: Harshini Weerasinghe, Michael Payne, Sally Beard, Alex Andrianopoulos
    Abstract:

    Organism-wide approaches examining the genetic mechanisms controlling growth and proliferation have proven to be a powerful tool in the study of pathogenic fungi. For many fungal pathogens techniques to study transcription and protein expression are particularly useful, and offer insights into infection processes by these species. Here we discuss the use of approaches such as differential display, suppression subtractive hybridization, microarray, RNA-seq, proteomics, genetic manipulation and infection models for the AIDS-defining pathogen Talaromyces Marneffei. Together these methods have broadened our understanding of the biological processes, and genes that underlie them, which are involved in switching between the saprophytic and pathogenic states of T. Marneffei, the maintenance of these two specialized cell types and its ability to cause disease.