+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Mucor circinelloides Thrives inside the Phagosome through an Atf-Mediated Germination Pathway



Mucor circinelloides Thrives inside the Phagosome through an Atf-Mediated Germination Pathway



Mbio 10(1)



Mucormycosis is an emerging fungal infection that is often lethal due to the ineffectiveness of current therapies. Here, we have studied the first stage of this infection-the germination of Mucor circinelloides spores inside phagocytic cells-from an integrated transcriptomic and functional perspective. A relevant fungal gene network is remodeled in response to phagocytosis, being enriched in crucial functions to survive and germinate inside the phagosome, such as nutritional adaptation and response to oxidative stress. Correspondingly, the phagocytic cells induced a specific proinflammatory and apoptotic response to the pathogenic strain. Deletion of fungal genes encoding putative transcription factors (atf1, atf2, and gcn4), extracellular proteins (chi1 and pps1), and an aquaporin (aqp1) revealed that these genes perform important roles in survival following phagocytosis, germination inside the phagosome, and virulence in mice. atf1 and atf2 play a major role in these pathogenic processes, since their mutants showed the strongest phenotypes and both genes control a complex gene network of secondarily regulated genes, including chi1 and aqp1 These new insights into the initial phase of mucormycosis define genetic regulators and molecular processes that could serve as pharmacological targets.IMPORTANCE Mucorales are a group of ancient saprophytic fungi that cause neglected infectious diseases collectively known as mucormycoses. The molecular processes underlying the establishment and progression of this disease are largely unknown. Our work presents a transcriptomic study to unveil the Mucor circinelloides genetic network triggered in fungal spores in response to phagocytosis by macrophages and the transcriptional response of the host cells. Functional characterization of differentially expressed fungal genes revealed three transcription factors and three extracellular proteins essential for the fungus to survive and germinate inside the phagosome and to cause disease in mice. Two of the transcription factors, highly similar to activating transcription factors (ATFs), coordinate a complex secondary gene response involved in pathogenesis. The significance of our research is in characterizing the initial stages that lead to evasion of the host innate immune response and, in consequence, the dissemination of the infection. This genetic study offers possible targets for novel antifungal drugs against these opportunistic human pathogens.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066462873

Download citation: RISBibTeXText

PMID: 30723131

DOI: 10.1128/mbio.02765-18


Related references

Isolation of Mucor circinelloides from a case of ulcerative mycosis of platypus (Ornithorhynchus anatinus), and a comparison of the response of Mucor circinelloides and Mucor amphibiorum to different culture temperatures. Medical Mycology 37(3): 201-206, 1999

Spores of Mucor ramosissimus, Mucor plumbeus and Mucor circinelloides and their ability to activate human complement system in vitro. Medical Mycology 48(2): 278-284, 2010

Mutants of the carotenoid biosynthetic pathway of Mucor circinelloides. Experimental Mycology. : 186-190, 1995

Physiological properties and fatty acid composition in Mucor circinelloides f. circinelloides. Antonie van Leeuwenhoek 71(3): 201-206, 1997

Agrobacterium tumefaciens-mediated transformation of Mucor circinelloides. Folia Microbiologica 50(5): 415-420, 2006

Effect of acetate and pH on sunflower oil assimilation by Mucor circinelloides f. circinelloides. Systematic and Applied Microbiology 22(1): 156-160, 1999

Enhanced sunflower oil utilization and gamma-linolenic acid production by Mucor circinelloides f.circinelloides CBS 108.16 in the presence of acetate. World Journal of Microbiology and Biotechnology 13(3): 357-358, 1997

Enhanced sunflower oil utilization and gamma-linolenic acid production by Mucor circinelloides f. circinelloides CBS 108.16 in the presence of acetate. World Journal of Microbiology & Biotechnology 13(3): 357-358, 1997

Gene fusions for the directed modification of the carotenoid biosynthesis pathway in Mucor circinelloides. Methods in Molecular Biology 898: 109-122, 2012

Outbreak of Invasive Wound Mucormycosis in a Burn Unit Due to Multiple Strains of Mucor circinelloides f. circinelloides Resolved by Whole-Genome Sequencing. Mbio 9(2), 2018

Expression Vectors and Gene Fusions for the Directed Modification of the Carotenoid Biosynthesis Pathway in Mucor circinelloides. Methods in Molecular Biology 1852: 239-256, 2018

Biosynthesis, characterization and enzymatic transesterification of single cell oil of Mucor circinelloides--a sustainable pathway for biofuel production. Bioresource Technology 181: 47-53, 2015

A non-canonical RNA degradation pathway suppresses RNAi-dependent epimutations in the human fungal pathogen Mucor circinelloides. Plos Genetics 13(3): E1006686, 2017

Expression of active mucor miehei aspartic protease in mucor circinelloides. Carlsberg Research Communications 52(4): 243-252, 1987

CRISPR-Cas9-mediated disruption of the HMG-CoA reductase genes of Mucor circinelloides and subcellular localization of the encoded enzymes. Fungal Genetics and Biology 2019, 2019