Trichosporon species now ranks as the second most common cause of disseminated yeast infections with a high mortality rate. Breakthrough trichosporonosis in patients receiving echinocandins therapy is being recognized...Trichosporon species now ranks as the second most common cause of disseminated yeast infections with a high mortality rate. Breakthrough trichosporonosis in patients receiving echinocandins therapy is being recognized recently. We present a case of breakthrough trichosporonosis with acute viral myocarditis while receiving caspofungin therapy. Trichosporon infection should be considered in patients, who have risk factors for invasive fungal infection and develop unexplained clinical manifestations of infection despite treatment with echinocandins.展开更多
Background: The clinical significance of the detection of Candida albicans on mucous membranes of the respiratory or intestinal tract from patients in intensive care units is still not finally clarified. Many patients...Background: The clinical significance of the detection of Candida albicans on mucous membranes of the respiratory or intestinal tract from patients in intensive care units is still not finally clarified. Many patients reveal colonization, although, despite increased risk, there are only a few invasive infections detectable. Therefore, antimycotic therapy in this setting is strongly discouraged. In reality, however, many patients receive antimycotics as a pre-emptive therapy. To elucidate this point, a literature research was performed. Results: In the light of new results on the pathogenicity of C.albicans, the recommendation not to treat should be discussed anew. Without becoming invasive, C.albicans influences the immune system negatively in an anti-inflammatory sense (Th2) by means of at least two distinct mechanisms [action on toll like receptors (TLR), production of farnesol], which will be discussed. Conclusion: It is believed that patients in the phase of CARS or MARS can be further endangered by concomitant colonization of mucous membranes by C.albicans, i.e., in the sense of an anti-inflammatory immune response. Treatment with azole preparations, like fluconazole, which interacts with ergosterol synthesis in this phase of the disease, may trigger an additional effect on the patient, through increase of farnesol concentration by way of a negative feedback. Results of animal experiments on the immune system and concomitant therapeutic consequences indicate the need for verification through clinical trials.展开更多
Pneumocandin B_(0)(PB_(0))is a lipohexapeptide synthesized by Glarea lozoyensis and serves as the precursor for the widely used antifungal drug caspofungin acetate(Cancidas®).However,the low titer of PB_(0)result...Pneumocandin B_(0)(PB_(0))is a lipohexapeptide synthesized by Glarea lozoyensis and serves as the precursor for the widely used antifungal drug caspofungin acetate(Cancidas®).However,the low titer of PB_(0)results in fermentation and purification costs during caspofungin production,limiting its widespread clinical application.Here,we engineered an efficient PB_(0)-producing strain of G.lozoyensis by systems metabolic engineering strategies,including multi-omics analysis and multilevel metabolic engineering.We overexpressed four rate-limiting enzymes:thioesterase GLHYD,two cytochrome P450s GLP450s,and chorismate synthase GLCS;knocked out two competing pathways responsible for producing 6-methylsalicylic acid and pyranidine E;and overexpressed the global transcriptional activator GLHYP.As a result,the PB_(0)titer increased by 108.7%to 2.63 g/L at the shake-flask level through combinatorial strategies.Our study provides valuable insights into achieving high-level production of PB_(0)and offers general guidance for developing efficient fungal cell factories to produce polyketide synthase-non-ribosomal peptide synthetase hybrid metabolites.展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30771939）.
文摘Trichosporon species now ranks as the second most common cause of disseminated yeast infections with a high mortality rate. Breakthrough trichosporonosis in patients receiving echinocandins therapy is being recognized recently. We present a case of breakthrough trichosporonosis with acute viral myocarditis while receiving caspofungin therapy. Trichosporon infection should be considered in patients, who have risk factors for invasive fungal infection and develop unexplained clinical manifestations of infection despite treatment with echinocandins.
文摘Background: The clinical significance of the detection of Candida albicans on mucous membranes of the respiratory or intestinal tract from patients in intensive care units is still not finally clarified. Many patients reveal colonization, although, despite increased risk, there are only a few invasive infections detectable. Therefore, antimycotic therapy in this setting is strongly discouraged. In reality, however, many patients receive antimycotics as a pre-emptive therapy. To elucidate this point, a literature research was performed. Results: In the light of new results on the pathogenicity of C.albicans, the recommendation not to treat should be discussed anew. Without becoming invasive, C.albicans influences the immune system negatively in an anti-inflammatory sense (Th2) by means of at least two distinct mechanisms [action on toll like receptors (TLR), production of farnesol], which will be discussed. Conclusion: It is believed that patients in the phase of CARS or MARS can be further endangered by concomitant colonization of mucous membranes by C.albicans, i.e., in the sense of an anti-inflammatory immune response. Treatment with azole preparations, like fluconazole, which interacts with ergosterol synthesis in this phase of the disease, may trigger an additional effect on the patient, through increase of farnesol concentration by way of a negative feedback. Results of animal experiments on the immune system and concomitant therapeutic consequences indicate the need for verification through clinical trials.
基金funded by the National Key R&D Program of China(2021YFC2102600)the National Natural Science Foundation of China(32370060 and 32070063)the Shenzhen Science and Technology Program(JCYJ20241202124932044).
文摘Pneumocandin B_(0)(PB_(0))is a lipohexapeptide synthesized by Glarea lozoyensis and serves as the precursor for the widely used antifungal drug caspofungin acetate(Cancidas®).However,the low titer of PB_(0)results in fermentation and purification costs during caspofungin production,limiting its widespread clinical application.Here,we engineered an efficient PB_(0)-producing strain of G.lozoyensis by systems metabolic engineering strategies,including multi-omics analysis and multilevel metabolic engineering.We overexpressed four rate-limiting enzymes:thioesterase GLHYD,two cytochrome P450s GLP450s,and chorismate synthase GLCS;knocked out two competing pathways responsible for producing 6-methylsalicylic acid and pyranidine E;and overexpressed the global transcriptional activator GLHYP.As a result,the PB_(0)titer increased by 108.7%to 2.63 g/L at the shake-flask level through combinatorial strategies.Our study provides valuable insights into achieving high-level production of PB_(0)and offers general guidance for developing efficient fungal cell factories to produce polyketide synthase-non-ribosomal peptide synthetase hybrid metabolites.
