UNASSIGNED: In addition to post-transplant lymphoproliferative disorders, it is necessary to be alert to the drug-resistant bacteria or fungal infection, especially Talaromyces marneffei, in kidney transplant patients who have failed antibiotic treatment and whose PET-CT indicates high metabolic mass in the transplanted kidney with a large number of other organs and lymph nodes.
UNASSIGNED: Talaromyces marneffei (TM) is a rare pathogenic fungus that primarily affects individuals with compromised immune systems. Post-transplant lymphoproliferative disorders (PTLD) are serious complications that can occur after solid organ and cell transplantation. Both TM infection and PTLD can invade the monocyte-macrophage system and often manifest as extranodal masses. This case report describes a kidney transplant patient who presented with symptoms of frequent, urgent, and painful urination over 6 months. Pulmonary CT scans revealed multiple nodules, and PET-CT demonstrated enlarged lymph nodes in the lungs and the transplanted kidney. The clinical manifestations closely mimicked those of PTLD. The confirmation of TM was achieved through pathogen metagenomic next-generation sequencing and renal biopsy. Unfortunately, despite receiving treatment with antifungal agents, anti-infective therapy, the patient\'s condition did not respond favorably, ultimately resulting in their unfortunate demise due to COVID-19.

OBJECTIVE: Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases. However, studies on Talaromyces marneffei detection using mNGS remain scarce. Therefore, this study aimed to explore the diagnostic performance of mNGS in T. marneffei.
METHODS: Between March 2021 and June 2023, patients who were discharged with a final diagnosis of talaromycosis, or confirmed T. marneffei infection by mNGS, culture or pathological examination were included in the study. Culture and mNGS were performed simultaneously for all patients. Clinical data were retrieved for analysis.
RESULTS: A total of 78 patients were enrolled, with 40 in the talaromycosis group and 38 in the suspected-talaromycosis group. In the talaromycosis group, mNGS showed a higher positivity rate(40/40, 100.0%) compared to culture(34/40, 85.0%)(P = 0.111). All patients in the suspected-talaromycosis group tested negative via culture, while mNGS yielded positive results. The T. marneffei reads in the talaromycosis group were significantly higher than in the suspected-talaromycosis group (4399 vs. 28, P < 0.001). In the suspected-talaromycosis group, of the four patients with low reads who did not receive antifungal therapy, one died and one lung lesion progressed; most patients(31/34, 91.2%) recovered after receiving appropriate antifungal therapy.
CONCLUSIONS: mNGS proves to be a rapid and highly sensitive method for detecting T. marneffei. Higher reads of T. marneffei correspond to a higher likelihood of infection. However, cases with low reads necessitate a comprehensive approach, integrating clinical manifestations, laboratory tests, and imaging examinations to confirm T. marneffei infection.

UNASSIGNED: Systemic dimorphic fungi pose a significant public health challenge, causing over one million new infections annually. The dimorphic transition between saprophytic mycelia and pathogenic yeasts is strongly associated with the pathogenesis of dimorphic fungi. However, despite the dynamic nature of dimorphic transition, the current omics studies focused on dimorphic transition primarily employ static strategies, partly due to the lack of suitable dynamic analytical methods.
UNASSIGNED: We conducted time-course transcriptional profiling during the dimorphic transition of Talaromyces marneffei, a model organism for thermally dimorphic fungi. To capture non-uniform and nonlinear transcriptional changes, we developed DyGAM-NS (dynamic optimized generalized additive model with natural cubic smoothing). The performance of DyGAM-NS was evaluated by comparison with seven other commonly used time-course analysis methods. Based on dimorphic transition induced genes (DTIGs) identified by DyGAM-NS, cluster analysis was utilized to discern distinct gene expression patterns throughout dimorphic transitions of T. marneffei. Simultaneously, a gene expression regulatory network was constructed to probe pivotal regulatory elements governing the dimorphic transitions.
UNASSIGNED: By using DyGAM-NS, model, we identified 5,223 DTIGs of T. marneffei. Notably, the DyGAM-NS model showcases performance on par with or superior to other commonly used models, achieving the highest F1 score in our assessment. Moreover, the DyGAM-NS model also demonstrates potential in predicting gene expression levels throughout temporal processes. The cluster analysis of DTIGs suggests divergent gene expression patterns between mycelium-to-yeast and yeast-to-mycelium transitions, indicating the asymmetrical nature of two transition directions. Additionally, leveraging the identified DTIGs, we constructed a regulatory network for the dimorphic transition and identified two zinc finger-containing transcription factors that potentially regulate dimorphic transition in T. marneffei.
UNASSIGNED: Our study elucidates the dynamic transcriptional profile changes during the dimorphic transition of T. marneffei. Furthermore, it offers a novel perspective for unraveling the underlying mechanisms of fungal dimorphism, emphasizing the importance of dynamic analytical methods in understanding complex biological processes.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by a hyperinflammatory syndrome and impairment of multiple organ systems. Talaromycosis marneffei (TSM) is an opportunistic infection mostly found in immunosuppressed populations, such as those with acquired immunodeficiency syndrome (AIDS), and is prevalent in southern China. However, HLH secondary to TSM is extremely rare and has only been reported in isolated cases. A 30-year-old patient with recurrent high fever and progressive cytopenia was diagnosed with HLH secondary to disseminated TSM with AIDS and Alpha-thalassemia. The patient remained in sustained remission without recurrence after effective treatment with antifungals and glucocorticoids.

UNASSIGNED: Talaromyces marneffei (TM) is the third most prevalent opportunistic infection in HIV-positive patients after tuberculosis and cryptococcosis. However, such infection of non-HIV individuals has rarely been reported.
UNASSIGNED: We describe a very rare case of a 52-year-old male who presented with a single space-occupying lesion on the right lung and was eventually diagnosed with pulmonary TM infection. The patient was HIV-negative and had liver cirrhosis with portal vein thrombosis. Lung tissue next-generation sequencing (NGS) revealed TM infection. We successfully treated the patient with voriconazole for 8 weeks and observed lesion absorption via subsequent CT. The patient consumed wild bamboo rats two months before admission. Mutations related to congenital immune deficiency were not detected by whole-exome sequencing.
UNASSIGNED: Early and timely diagnosis is critical for improving patient prognosis. NGS plays a vital role in the diagnosis of pulmonary TM infection in patients. To our knowledge, this is the first published case of pulmonary TM infection in an HIV-negative patient with liver cirrhosis.

UNASSIGNED: Talaromycosis is a serious opportunistic infectious disease caused by Talaromyces marneffei, which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death.
UNASSIGNED: Both patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for T. marneffei. T. marneffei was detected in the blood culture of case 2, with infection of Candida parapsilosis and Pneumocystis jirovecii. Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy.
UNASSIGNED: Talaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.

Anti-interferon-γ autoantibody (AIGA) syndrome may be the basis of disseminated Talaromyces marneffei infection in human immunodeficiency virus (HIV)-negative adults. However, the pathogenesis of Th1 cell immunity in T. marneffei infection with AIGA syndrome is unknown. A multicenter study of HIV-negative individuals with T. marneffei infection was conducted between September 2018 and September 2020 in Guangdong and Guangxi, China. Patients were divided into AIGA-positive (AP) and AIGA-negative (AN) groups according to the AIGA titer and neutralizing activity. The relationship between AIGA syndrome and Th1 immune deficiency was investigated by using AP patient serum and purification of AIGA. Fifty-five HIV-negative adults with disseminated T. marneffei infection who were otherwise healthy were included. The prevalence of AIGA positivity was 83.6%. Based on their AIGA status, 46 and 9 patients were assigned to the AP and AN groups, respectively. The levels of Th1 cells, IFN-γ, and T-bet were higher in T. marneffei-infected patients than in healthy controls. However, the levels of CD4+ T-cell STAT-1 phosphorylation (pSTAT1) and Th1 cells were lower in the AP group than in the AN group. Both the serum of patients with AIGA syndrome and the AIGA purified from the serum of patients with AIGA syndrome could reduce CD4+ T-cell pSTAT1, Th1 cell differentiation and T-bet mRNA, and protein expression. The Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients. Inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome.IMPORTANCEThe pathogenesis of Th1 cell immunity in Talaromyces marneffei infection with anti-interferon-γ autoantibody (AIGA) syndrome is unknown. This is an interesting study addressing an important knowledge gap regarding the pathogenesis of T. marneffei in non-HIV positive patients; in particular patients with AIGA. The finding of the Th1 cell immune response plays a pivotal role in defense against T. marneffei infection in HIV-negative patients, and inhibition of the Th1 cell immune response may be an important pathological effect of AIGA syndrome, which presented in this research could help bridge the current knowledge gap.

UNASSIGNED: Talaromyces marneffei is prevalent in South Asia. Latent Talaromyces marneffei infection of travellers make the diagnosis difficult. There are similarities in clinical manifestations between Talaromyces marneffei infection and lymphoma. Brain abscess is a rare form of Talaromyces marneffei infection.
UNASSIGNED: We reported a very rare case of a 19-year-old man with HIV infection who suffered from a brain mass and lymphadenopathy. His blood culture, bone marrow culture and sputum culture all grew Talaromyces marneffei. One month after treatment with voriconazole, the symptoms improved except brain mass. Surgical incision of the brain mass showed a compact mass, and pathological analysis showed the coexisting Talaromyces marneffei abscess and lymphoma. The patient is currently in a stable condition after receiving antifungal therapy and chemotherapy.
UNASSIGNED: Based on a case report of a traveller who suffered from a brain mass of Talaromyces marneffei abscess and lymphoma after a visit to an endemic area, this review summarized the cases where there was confusion between lymphoma and the brain abscess of Talaromyces marneffei. Talaromyces marneffei infection can be found globally due to the increasing number of international travels. Talaromyces marneffei infection and lymphoma had similar characteristics which is easy to misdiagnose in clinic. Infection may also be accompanied by tumors, especially in patients infected with HIV. The manifestations and imaging of brain abscess of Talaromyces marneffei were not characteristic in different patients.

Talaromyces marneffei (TM) immune evasion is an important factor leading to the high mortality rate of Penicilliosis marneffei. N6 -methyladenosine (m6 A) plays important roles in host immune response to various pathogen infections, yet its role in TM and HIV/TM coinfection remains largely unexplored. Here we reported genome-wide transcriptional m6 A profiles of TM mono-infection and HIV/TM coinfection. Our finding revealed dynamic alterations in global m6 A levels and upregulation of the m6 A reader YTH N6 -methyladenosine RNA binding protein C2 (YTHDC2) in TM-infected macrophages. Knockdown of YTHDC2 in TM-infected cells showed an elevated expression of TLR2 through m6 A-dependence, along with upregulation of TNF-α and IL1-β. Overall, we characterized the m6 A profiles of the host and fungus before and after TM infection, and demonstrated that YTHDC2 mediates the key m6 A site of TLR2 to exert its function. These findings provide new insights into the underlying mechanisms and novel therapeutic approaches for TM diseases.

Mangrove-derived actinomycetes represent a rich source of novel bioactive natural products in drug discovery. In this study, four new polyene macrolide antibiotics antifungalmycin B-E (1-4), along with seven known analogs (5-11), were isolated from the fermentation broth of the mangrove strain Streptomyces hiroshimensis GXIMD 06359. All compounds from this strain were purified using semi-preparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity-guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds exhibited broad-spectrum antifungal activity against Talaromyces marneffei with minimum inhibitory concentration (MIC) values being in the range of 2-128 μg/mL except compound 2. This is the first report of polyene derivatives produced by S. hiroshimensis as bioactive compounds against T. marneffei. In vitro studies showed that compound 1 exerted a significantly stronger antifungal activity against T. marneffei than other new compounds, and the antifungal mechanism of compound 1 may be related to the disrupted cell membrane, which causes mitochondrial dysfunction, resulting in leakage of intracellular biological components, and subsequently, cell death. Taken together, this study provides a basis for compound 1 preventing and controlling talaromycosis.