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      Control of morphology and virulence by ADP-ribosylation factors (Arf) in Mucor circinelloides.

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          Abstract

          Mucor circinelloides is a dimorphic fungus used to study cell differentiation that has emerged as a model to characterize mucormycosis. In this work, we identified four ADP-ribosylation factor (Arf)-encoding genes (arf1-arf4) and study their role in the morphogenesis and virulence. Arfs are key regulators of the vesicular trafficking process and are associated with both growth and virulence in fungi. Arf1 and Arf2 share 96% identity and Arf3 and Arf4 share 89% identity, which suggests that the genes arose through gene-duplication events in M. circinelloides. Transcription analysis revealed that certain arf genes are affected by dimorphism of M. circinelloides, such as the arf2 transcript, which was accumulated during yeast development. Therefore, we created knockout mutants of four arf genes to evaluate their function in dimorphism and virulence. We found that both arf1 and arf2 are required for sporulation, but these genes also perform distinct functions; arf2 participates in yeast development, whereas arf1 is involved in aerobic growth. Conversely, arf3 and arf4 play only minor roles during aerobic growth. Moreover, we observed that all single arf-mutant strains are more virulent than the wild-type strain in mouse and nematode models, with the arf3 mutant being most virulent. Lastly, arf1/arf2 and arf3/arf4 double mutations produced heterokaryon strains that did not reach the homokaryotic state, indicating that these genes participate in essential and redundant functions. Overall, this work reveals that Arfs proteins regulate important cellular processes in M. circinelloides such as morphogenesis and virulence, laying the foundation to characterize the molecular networks underlying this regulation.

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          Author and article information

          Journal
          Curr. Genet.
          Current genetics
          Springer Nature
          1432-0983
          0172-8083
          Dec 20 2017
          Affiliations
          [1 ] Laboratorio de Diferenciación Celular, Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, 58030, Morelia, Michoacan, Mexico.
          [2 ] Departamento de Genética y Microbiología, Facultad de Biologia, Universidad de Murcia, 30100, Murcia, Spain.
          [3 ] Facultad de Químico Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacan, Mexico.
          [4 ] Laboratorio Estatal de Salud Pública del Estado de Michoacán, 58279, Morelia, Michoacan, Mexico.
          [5 ] Laboratorio de Diferenciación Celular, Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, 58030, Morelia, Michoacan, Mexico. victor_meza2004@yahoo.com.mx.
          Article
          10.1007/s00294-017-0798-0
          10.1007/s00294-017-0798-0
          29264641
          08e9ee0e-619b-4cbd-8237-1f2906d81272
          History

          Vesicle trafficking,Secretion,Mucor,Fungal virulence,Arf protein,ADP-ribosylation factor

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