Calcineurin A Is Essential in the Regulation of Asexual Development, Stress Responses and Pathogenesis in Talaromyces marneffei

Zheng, Yanqing; Pan, Kai-Su; Latgé, Jean‐Paul; Andrianopoulos, Alex; Luo, Hong; Yan, Rufan; Wei, Jin-Ying; Huang, Chunyang; Cao, Cunwei

doi:10.3389/fmicb.2019.03094

Cited by 8 publications

(6 citation statements)

References 52 publications

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“…[96][97][98] and Pacoccidiodes brasiliensis [99]. Recent studies reveal a role of calcineurin in growth and virulence of T. marneffei [100]. In T. marneffei, deletion of the cnaA gene resulted in substantial defects in conidiation, germination, morphogenesis, cell wall integrity, and tolerance to several stresses.…”

Section: Iron and Calcium Are Essential Cations Required For Growth A...mentioning

confidence: 99%

Talaromyces marneffei Infection: Virulence Factors and Rapid Diagnostics

Youngchim¹

2022

Infectious Diseases

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Talaromyces (Penicillium) marneffei is a thermally dimorphic fungus that causes talaromycosis, and the pathogen is found throughout tropical and subtropical Asia. T. marneffei has specifically emerged as an opportunistic fungal pathogen in individuals with advanced HIV disease and, to a lesser extent, other immunocompromised conditions, but more recently talaromycosis is increasingly described in immunocompetent people. Due to the high mortality rate of up to 50%, understanding T. marneffei interactions with host immune responses and diagnostic modalities is vital to the development of strategies to reduce morbidity and mortality. In this chapter, we describe T. marneffei virulence factors that enhance the fungus’ capacity for survival and growth in the host to lead to disease. We also discuss approaches for early diagnosis, which are essential to reduce the mortality rate in talaromycosis. Talaromycosis remains a neglected disease, but advances in our understanding of host-pathogen dynamics as well as the ongoing development of new diagnostic approaches are poised to enhance our capacity to combat this disease.

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Section: Iron and Calcium Are Essential Cations Required For Growth A...mentioning

confidence: 99%

Talaromyces marneffei Infection: Virulence Factors and Rapid Diagnostics

Youngchim¹

2022

Infectious Diseases

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“…Amphotericin B is the rst-line drug recommended to treat T. marneffei [1]. Meanwhile, voriconazole is effective against T. marneffei [29][30][31][32][33]. Huang et al [30] reported similar response rates with voriconazole and amphotericin B as induction therapy for Talaromycosis in patients with HIV/AIDS, but voriconazole had a shorter induction time (11-13 days vs. two weeks).…”

Section: Discussionmentioning

confidence: 99%

Metagenomics-Based Diagnosis and Monitoring Treatment of Disseminated Talaromyces Marneffei Infection

Xie

et al. 2021

Preprint

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Background: The diagnosis of T. marneffei infection remains challenging due to its non-specific clinical presentations and the inadequate performance of conventional diagnostic methods. Meanwhile, there is no good indicator to monitor when induction treatment should switch to consolidation treatment.Case summary: A 53-year-old male patient presented with a one-week history of high fever on March 21, 2019, 10 years after a liver transplant. A chest CT showed multiple pulmonary nodules. Blood culture revealed T. marneffei. After two weeks of intravenous treatment of voriconazole and caspofungin, the patient was discharged without fever and was given oral voriconazole on April 8. Two days later, the patient had a fever again. The patient was fever-free soon after intravenous voriconazole. However, a high fever occurred three days later. Cultures of blood and sputum were negative. Metagenomics next-generation sequencing (mNGS) detected T. marneffei sequences in blood and Enterococcus faecium sequences in sputum. Despite the use of caspofungin and linezolid, the patient maintained a daily fever of 38.5°C. Chest CT revealed that pulmonary nodules were growing in size and number. After administering Amphotericin B, the temperature quickly returned to normal. Liposomal amphotericin B was used due to increased creatinine. When the sequence of T. marneffei turned negative in the blood, the patient was discharged on May 24 and received 14-week oral voriconazole without relapse. Conclusion: mNGS can directly detect the sequence of T. marneffei in the blood. Consequently, mNGS is a powerful technique in precise diagnosis and a good monitoring technique for treating disseminated T. marneffei.

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“…Exposures to 254 nm UV irradiation for 5, 10, and 15 min were also tested for UV resistance. All cultures were incubated for 14 days at 25°C.Based on references [ 10 , 18 ] and pre-experiments, the concentrations of KCl, H 2 O 2 , SNAP, menadione (VitK), and sorbitol were selected. The ability of melanin recovery in albino strains and pigmented strains were cultured on PDA with 50 mg/L tricyclazole at 25°C for 14 days.…”

Section: Methodsmentioning

confidence: 99%

Deletion C-terminal thioesterase abolishes melanin biosynthesis, affects metabolism and reduces the pathogenesis of Fonsecaea monophora

Huang

et al. 2022

PLoS Negl Trop Dis

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Dematiaceous Fonsecaea monophora is one of the major pathogens of chromoblastomycosis. It has been well established that melanization is catalyzed by the type I polyketide synthase (PKS) in F. monophora. Multidomain protein Type I PKS is encoded by six genes, in which the last enzyme thioesterase (TE) catalyzes the cyclization and releases polyketide. Two PKS genes AYO21_03016 (pks1) and AYO21_10638 have been found in F. monophora and both PKS loci have the same gene arrangement but the TE domain in AYO21_10638 is truncated at 3’- end. TE may be the key enzyme to maintain the function of pks1. To test this hypothesis, we constructed a 3’-end 500 bp deletion mutant of AYO21_03016 (Δpks1-TE-C500) and its complemented strain. We profiled metabolome of this mutant and analyzed the consequences of impaired metabolism in this mutant by fungal growth in vitro and by pathogenesis in vivo. Compared with wild-type strain, we found that the mutant repressed pks1 expression and other 5 genes expression levels were reduced by more than 50%, perhaps leading to a corresponding melanin loss. The mutant also reduced sporulation and delayed germination, became vulnerable to various environmental stresses and was less resistance to macrophage or neutrophil killings in vitro, and less virulence in mice footpad model. Metabolomic analysis indicated that many metabolites were remarkably affected in Δpks1-TE-C500, in particular, an increased nicotinamide and antioxidant glutathione. In conclusion, we confirmed the crucial role of C-terminal TE in maintaining fully function of pks1 in F. monophora. Deletion of TE negatively impacts on the synthesis of melanin and metabolites that eventually affect growth and virulence of F. monophora. Any potential inhibitor of TE then could be a novel antifungal target for drug development.

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Calcineurin A Is Essential in the Regulation of Asexual Development, Stress Responses and Pathogenesis in Talaromyces marneffei

Cited by 8 publications

References 52 publications

Talaromyces marneffei Infection: Virulence Factors and Rapid Diagnostics

Talaromyces marneffei Infection: Virulence Factors and Rapid Diagnostics

Metagenomics-Based Diagnosis and Monitoring Treatment of Disseminated Talaromyces Marneffei Infection

Deletion C-terminal thioesterase abolishes melanin biosynthesis, affects metabolism and reduces the pathogenesis of Fonsecaea monophora

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