Talaromyces marneffei (TSM) is a temperature-dependent dimorphic fungus endemic to Southeast Asia and southern China. As the number of people at risk of TSM infection continues to increase, the clinical manifestations are becoming increasingly complex, posing challenges for clinical management. In this study, we analyzed the medical records of 99 patients (71 human immunodeficiency virus [HIV]-positive and 28 HIV-negative) diagnosed with TSM infection from January 1, 2017, to December 31, 2022, in southern China and compared the clinical manifestations in HIV-positive and HIV-negative patients. Most patients (83/99, 84%) were male. The incidence of skin and soft tissue involvement (48% vs. 21%, P = .016); disseminated infection with blood circulation, hematopoietic, lymphatic, alimentary, or central nervous system involvement (69% vs. 36%, P = .002); and gastrointestinal bleeding (33% vs. 9%, P = .023) was higher in the HIV-positive group than the HIV-negative group. The HIV-positive group also had significantly higher alanine aminotransferase (ALT) levels (31 [26-42] vs. 14 [11-16] U/l, P < .001) and ALT/aspartate transaminase ratio (1.9 [1.5-2.2] vs. 1.3 [1.1-1.6], P = .006) than the HIV-negative group. The time to diagnosis (5.5 ± 1.1 vs. 5.1 ± 1.4 days, P = .103), antifungal regimen (P = .278), case fatality rate (20% vs. 21%, P = .849), and relapse/reinfection rate (11% vs. 19%, P = .576) did not differ significantly between the HIV-positive and HIV-negative groups. Poor antiretroviral therapy adherence (OR = 26.19, 95%CI 3.26-210.70, P = .002), advanced age (OR = 1.13, 95%CI 1.03-1.23, P = .010), and Epstein-Barr virus co-infection (OR = 37.13, 95%CI 3.03-455.64, P = .005) were independent risk factors for all-cause mortality from TSM infection in HIV-positive patients. Overall, the predominant infection sites, clinical manifestations, and complications of TSM infection differed by HIV status. However, with prompt diagnosis and appropriate treatment, HIV-positive patients with TSM infection can have similar outcomes to HIV-negative patients.
There are certain differences in the clinical features, sites of infection, and associated complications of Talaromyces marneffei infection between individuals with and without human immunodeficiency virus. It is necessary to accurately identify individuals at high risk to enable prompt diagnosis and standardized treatment.

OBJECTIVE: Talaromyces marneffei is an emerging pathogen, and the number of infections in HIV-negative individuals is rapidly increasing. Nevertheless, there is no sufficient comprehensive report on this issue, and awareness needs to be raised among clinicians.
METHODS: We analyzed the differences in the clinical data of patients who are HIV-negative and HIV-positive with Talaromyces marneffei infection (TMI) from 2018 to 2022.
RESULTS: A total of 848 patients were included, among whom 104 were HIV-negative. The obvious differences between the HIV-positive and HIV-negative groups were as follows: (i) the patients who are HIV-negative were older and more likely to exhibit cough and rash, (ii) the time in days from symptom onset to diagnosis among patients who are HIV-negative was longer, (iii) the laboratory findings and radiological presentations seemed more severe in patients who are HIV-negative, (iv) differences were observed regarding the underlying conditions and co-infection pathogens, and correlation analysis showed that correlations existed for many indicators, (v) and persistent infection was more likely to occur in patients who are HIV-negative.
CONCLUSIONS: TMI in patients who are HIV-negative differs from that in patients who are HIV-positive in many aspects, and more investigations are needed. Clinicians should be more aware of TMI in patients who are HIV-negative.

BACKGROUND: Talaromyces marneffei (T. Marneffei) infection is considered as an indicator of immunosuppression in immunocompromised individuals, leading to multiple organ damage. Our study aimed to evaluate both the clinical characteristics and immunological features of pediatric patients infected with T. marneffei from our institute, providing novel insights into diagnosis and treatment for this life-threatening disease.
METHODS: Thirteen pediatric patients with T. marneffei infection were enrolled in Guangzhou Women and Children\'s Medical Center during 2012 to 2020. Clinical data and laboratory findings were collected and further analyzed. Pearson correlation coefficient was calculated to determine the relationship between serum immunoglobulins (Igs) levels and white blood cell count, or the absolute lymphocyte count.
RESULTS: Patients were diagnosed as having T. Marneffei infection mainly based on the results of fungal culture and Gram stain of specimens. The most common presentations were fever (69%), pneumonia (38%) and immunodeficiency (38%). The total levels of Igs (IgE, IgA, and IgM) were positively correlated with both white blood cell count and absolute lymphocyte count.
CONCLUSIONS: Serum Ig expression Pattern in patients diagnosed with T. marneffei infection might serve as an effective prognostic marker which would help with the development of early interventions for children with this fatal disease.

Disseminated talaromycosis caused by Talaromyces marneffei is a life-threatening opportunistic infection. Although amphotericin B deoxycholate (dAmB) remains the first-line induction treatment, voriconazole can also be used. However, no clinical trials have compared dAmB and voriconazole in the administration of talaromycosis. We retrospectively evaluated the efficacy and safety of voriconazole or dAmB as induction therapy for talaromycosis in HIV-infected patients. We enrolled HIV-infected patients with a confirmed Talaromyces marneffei infection who received intravenous dAmB (0.6 to 0.7 mg/kg daily for 2 weeks) or voriconazole (6 mg/kg every 12 h on day 1 and 4 mg/kg every 12 h afterward) as induction therapy, followed by oral itraconazole as consolidation and maintenance therapy. Drug efficacy was evaluated based on response rate. Drug safety was evaluated based on the occurrence of adverse events. In total, 58 patients who received voriconazole and 82 who received dAmB were enrolled from two hospitals. The voriconazole and dAmB treatment groups had similar response rates at the primary and follow-up efficacy evaluations. However, the durations of induction antifungal therapy and hospital stay were shorter for patients in the voriconazole group than in the dAmB group. Few adverse reactions occurred in either the voriconazole or dAmB group. Our retrospective study indicated that voriconazole is an effective and safe induction antifungal drug for HIV-associated disseminated talaromycosis. The duration of induction treatment with voriconazole was shorter, indicating its potential as a better choice in clinical practice. The duration of voriconazole induction therapy is 11 to 13 days.

Preasperterpenoid A, featuring a 5/7/(3)6/5 pentacyclic structure, is a C25 sesterterpenoid produced by Penicillium verruculosum. The results of density functional calculations on putative biosynthetic carbocation cyclization/rearrangements leading to preasperterpenoid A revealed a highly concerted four-step cyclization mechanism. Interestingly, two secondary carbocation structures were obtained as minima, but appeared almost as shoulders in the energy profile, and may represent essentially transient structures during the highly concerted reaction.

Phospholipase B (EC 3.1.1.5) are a distinctive group of enzymes that catalyzes the hydrolysis of fatty acids esterified at the sn-1 and sn-2 positions forming free fatty acids and lysophospholipids. The structural information and catalytic mechanism of phospholipase B are still not clear. Herein, we reported a putative phospholipase B (TmPLB1) from Talaromyces marneffei GD-0079 synthesized by genome mining library. The gene (TmPlb1) was expressed and the TmPLB1 was purified using E. coli shuffle T7 expression system. The putative TmPLB1 was purified by affinity chromatography with a yield of 13.5%. The TmPLB1 showed optimum activity at 35 °C and pH 7.0. The TmPLB1 showed enzymatic activity using Lecithin (soybean > 98% pure), and the hydrolysis of TmPLB1 by 31P NMR showed phosphatidylcholine (PC) as a major phospholipid along with lyso-phospholipids (1-LPC and 2-LPC) and some minor phospholipids. The molecular modeling studies indicate that its active site pocket contains Ser125, Asp183 and His215 as the catalytic triad. The structure dynamics and simulations results explained the conformational changes associated with different environmental conditions. This is the first report on biochemical characterization and structure dynamics of TmPLB1 enzyme. The present study could be helpful to utilize TmPLB1 in food industry for the determination of food components containing phosphorus. Additionally, such enzyme could also be useful in Industry for the modifications of phospholipids.

The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005-2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35-0.73). CTX reduced TM incidence in all CD4+ cell subgroups (<50 cells/μL, 50-99 cells/μL, 100-199 cells/μL), with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/μL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

The process economics of fermentable sugar production is dependent on the performance of cellulase cocktail on realistic lignocellulosic biomass and their capability to be recovered and recycled. Feasibility studies were conducted to enhance the digestibility of acid pretreated sugarcane bagasse using novel cellulase cocktail obtained from stable mutant UV-8 of Talaromyces verruculosus IIPC 324 in presence of lignin blocking additives. PEG 6000 was shortlisted as the best additive as it could simultaneously enhance saccharification and overall cellulase recoveries namely cellobiohydrolase, endoglucanase and cellobiase. Addition of 0.3 g PEG 6000/g acid-insoluble lignin content, resulted in 55% and 49.2% saccharification yields in terms of reducing sugars and glucose respectively using this cellulase cocktail (25 mg protein/g cellulose content) after 72 h from acid pretreated sugarcane bagasse loaded at 7.5%. The study also suggested that the endoglucanase of this mutant was unique with high desorption capability as 85% activity was observed in the saccharified broth devoid of any lignin blocking additive. At its optimum concentration, PEG 6000 was able to retain 94 ± 0.79% cellobiohydrolase I and 97.97 ± 1.16% cellobiase enzyme in the saccharified broth which were otherwise lost in residual biomass by ∼80%, in the absence of this polymeric additive. These results suggest that PEG 6000 was the most promising facilitator for recycling of cellulases obtained from mutant UV-8 of Talaromyces verruculosus IIPC 324 in particular. It paved a way towards the production of cheaper fermentable sugars which serve as a starting raw material for the production of green chemicals and fuels.

OBJECTIVE: Talaromyces marneffei is an opportunistic infection with high morbidity among human immunodeficiency virus (HIV)/AIDS patients in Southeast Asia and southern China. Its effects on mortality in HIV/AIDS patients has not been clearly elucidated.
METHODS: We conducted a retrospective cohort study of hospitalized HIV-infected individuals at the Fourth People\'s Hospital of Nanning, Guangxi, China during 2012-2015. Kaplan-Meier analyses were used to calculate the cumulative mortality. Cox proportional hazard models and 1:1 propensity score matching (PSM) were used to evaluate the effects of T. marneffei infection on mortality of HIV/AIDS patients.
RESULTS: In total, 6791 HIV/AIDS patients were included, 1093 of them (16.1%) with documented T. marneffei co-infection. The mortality of T. marneffei-infected patients (25.0 per 100 person-months, 95% CI 21.5-26.7) was the highest among all AIDS-associated complications and was significantly higher than that of T. marneffei-uninfected HIV/AIDS patients (13.8 per 100 person-months, 95% CI 12.5-15.1; adjusted hazard ratio (AHR) 1.80, 95% CI 1.48-2.16). The results using PSM were similar (AHR 4.52 95% CI 2.43-8.42). The mortality of T. marneffei-infected patients was also significantly higher than that of patients without any complications. When stratified by demographic characteristics, T. marneffei infection has higher mortality risk in all stratifications. Co-infection with T. marneffei carries a higher mortality risk in patients at any CD4+ T-cell count.
CONCLUSIONS: Talaromyces marneffei infection is commonly found in hospitalized HIV/AIDS patients in southern China and was associated with a higher mortality rate than most HIV-associated complications. These results highlight the need for improved diagnosis, treatment and prevention of infection by this neglected fungal pathogen in southern China.

OBJECTIVE: To improve the diagnosis and treatment of Penicilliosis marneffei without human immunodeficiency virus infection.
METHODS: Analyze and review the clinical features, diagnosis and treatment of six cases of P. marneffei without human immunodeficiency virus infection at The First Affiliated Hospital of Fujian Medical University.
RESULTS: Two cases were diagnosed in the ENT Department, three cases in the respiratory department and one case in the dermatological department. Penicillium marneffei infection was confirmed by sputum culture, blood culture and tissue biopsy. After definite diagnosis, one refused further treatment, and others showed significant improvement.
CONCLUSIONS: Penicilliosis marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve early diagnosis and appropriate treatment, doubtful cases should be alerted for the diagnoses as P. marneffei.