| Reference | 1. PLoS One. 2017 May 9;12(5):e0177050. doi: 10.1371/journal.pone.0177050. eCollection 2017.<br />
Temperature during conidiation affects stress tolerance, pigmentation, and trypacidin accumulation in the conidia of the airborne pathogen Aspergillus fumigatus.<br />
Hagiwara D(1), Sakai K(1), Suzuki S(2), Umemura M(3), Nogawa T(4), Kato N(4), Osada H(4), Watanabe A(1), Kawamoto S(1), Gonoi T(1), Kamei K(1).<br />
Author information:<br />
(1)Medical Mycology Research Center (MMRC), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan. (2)National Food Research Institute (NFRI), 2-1-12 Kan-nondai, Tsukuba, Ibaraki, Japan. (3)National Institute of Advanced Industrial Science and Technology (AIST), 17-2-1 Higashi-Nijo, Tsukisamu, Toyohira-ku, Sapporo, Japan. (4)RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.<br />
Asexual spores (conidia) are reproductive structures that play a crucial role in fungal distribution and survival. As fungal conidia are, in most cases, etiological agents of plant diseases and fungal lung disease, their stress resistance and interaction with their hosts have drawn increasing attention. In the present study, we investigated whether environmental temperature during conidiation affects the stress tolerance of the conidia of the human pathogenic fungus Aspergillus fumigatus. Conidia from a 25°C culture showed a lower tolerance to heat (60°C) and oxidative (H2O2) stresses and a marked resistance to ultraviolet radiation exposure, compared with those produced at 37 and 45°C. The accumulation of trehalose was lower in the conidia from the 25°C culture. Furthermore, the conidia from the 25°C culture showed darker pigmentation and increased transcripts of dihydroxynaphthalene (DHN)-melanin biosynthesis-related genes (i.e., pksP, arp1, and arp2). An RNA-sequencing analysis revealed that the transcription level of the trypacidin (tpc) gene cluster, which contains 13 genes, was sharply and coordinately activated in the conidia from the 25°C culture. Accordingly, trypacidin was abundant in the conidia from the 25°C culture, whereas there was little trypacidin in the conidia from the 37°C culture. Taken together, these data show that the environmental temperature during conidiation affects conidial properties such as stress tolerance, pigmentation, and mycotoxin accumulation. To enhance our knowledge, we further explored the temperature-dependent production of DHN-melanin and trypacidin in clinical A. fumigatus isolates. Some of the isolates showed temperature-independent production of DHN-melanin and/or trypacidin, indicating that the conidia-associated secondary metabolisms differed among the isolates.<br />
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2. Appl Microbiol Biotechnol. 2015 Dec;99(23):10151-61. doi: 10.1007/s00253-015-6898-1. Epub 2015 Aug 18.<br />
Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus.<br />
Mattern DJ(1)(2), Schoeler H(1)(2), Weber J(1)(2), Novohradská S(1)(2), Kraibooj K(2)(3), Dahse HM(4), Hillmann F(1), Valiante V(5), Figge MT(2)(3), Brakhage AA(6)(7).<br />
Author information:<br />
(1)Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany. (2)Friedrich Schiller University Jena, Jena, Germany. (3)Department of Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany. (4)Department of Infection Biology, Leibniz Institute for Infection Biology and Natural Product Research (HKI), Jena, Germany. (5)Leibniz Junior Research Group – Biobricks of Microbial Natural Product Syntheses, Jena, Germany. (6)Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Beutenbergstrasse 11a, 07745, Jena, Germany. [email protected]. (7)Friedrich Schiller University Jena, Jena, Germany. [email protected].<br />
The opportunistic human pathogen Aspergillus fumigatus produces numerous different natural products. The genetic basis for the biosynthesis of a number of known metabolites has remained unknown. The gene cluster encoding for the biosynthesis of the conidia-bound metabolite trypacidin is of particular interest because of its antiprotozoal activity and possible role in the infection process. Here, we show that the genes encoding the biosynthesis enzymes of trypacidin reside within an orphan gene cluster in A. fumigatus. Genome mining identified tynC as an uncharacterized polyketide synthase with high similarity to known enzymes, whose products are structurally related to trypacidin including endocrocin and fumicycline. Gene deletion of tynC resulted in the complete absence of trypacidin production, which was fully restored when the mutant strain was complemented with the wild-type gene. When confronted with macrophages, the tynC deletion mutant conidia were more frequently phagocytosed than those of the parental wild-type strain. This was also found for phagocytic amoebae of the species Dictyostelium discoideum, which showed increased phagocytosis of ΔtynC conidia. Both macrophages and amoebae were also sensitive to trypacidin. Therefore, our results suggest that the conidium-bound trypacidin could have a protective function against phagocytes both in the environment and during the infection process.<br />
3.<span style="font-family: Arial, sans-serif; font-size: 13px;">Balan, J., et al. "Antiprotozoal Antibiotics. II Isolation and Characterization of Trypacidin, A New Antibiotic, Active Against Trypanosoma Cruzi and Toxoplasma Gondii." </span><i style="font-family: Arial, sans-serif; font-size: 13px;">The Journal of Antibiotics, Series A</i><span style="font-family: Arial, sans-serif; font-size: 13px;"> 16.4 (1963): 157-160.</span>
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