scholarly journals GPI Anchored Proteins in Aspergillus fumigatus and Cell Wall Morphogenesis

Author(s):  
Marketa Samalova ◽  
Paul Carr ◽  
Mike Bromley ◽  
Michael Blatzer ◽  
Maryse Moya-Nilges ◽  
...  
2019 ◽  
Vol 21 (12) ◽  
Author(s):  
Nicolas Millet ◽  
Maryse Moya‐Nilges ◽  
Martin Sachse ◽  
Jacomina Krijnse Locker ◽  
Jean‐Paul Latgé ◽  
...  

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Isabella Luísa da Silva Gurgel ◽  
Karina Talita de Oliveira Santana Jorge ◽  
Nathália Luísa Sousa de Oliveira Malacco ◽  
Jéssica Amanda Marques Souza ◽  
Marina Campos Rocha ◽  
...  

ABSTRACT Aspergillus fumigatus is a filamentous fungus which causes invasive pulmonary aspergillosis in immunocompromised individuals. In fungi, cell signaling and cell wall plasticity are crucial for maintaining physiologic processes. In this context, Msb2 is an important signaling mucin responsible for activation of a variety of mitogen-activated protein kinase (MAPK)-dependent signaling pathways that regulate cell growth in several organisms, such as the cell wall integrity (CWI) pathway. Here, we aimed to characterize the MSB2 homologue in A. fumigatus. Our results showed that MsbA plays a role in the vegetative and reproductive development of the fungus, in stress adaptation, and in resistance to antifungal drugs by modulating the CWI pathway gene expression. Importantly, cell wall composition is also responsible for activation of diverse receptors of the host immune system, thus leading to a proper immune response. In a model of acute Aspergillus pulmonary infection, results demonstrate that the ΔmsbA mutant strain induced less inflammation with diminished cell influx into the lungs and lower cytokine production, culminating in increased lethality rate. These results characterize for the first time the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis and an important regulator of virulence. IMPORTANCE Aspergillus fumigatus is an opportunistic fungus with great medical importance. During infection, Aspergillus grows, forming hyphae that colonize the lung tissue and invade and spread over the mammal host, resulting in high mortality rates. The knowledge of the mechanisms responsible for regulation of fungal growth and virulence comprises an important point to better understand fungal physiology and host-pathogen interactions. Msb2 is a mucin that acts as a sensor and an upstream regulator of the MAPK pathway responsible for fungal development in Candida albicans and Aspergillus nidulans. Here, we show the role of the signaling mucin MsbA in the pathogen A. fumigatus, as a core sensor for cell wall morphogenesis, fungal growth, and virulence. Moreover, we show that cell wall composition, controlled by MsbA, is detrimental for fungal recognition and clearance by immune cells. Our findings are important for the understanding of how fungal sensors modulate cell physiology.


Microbiology ◽  
2006 ◽  
Vol 152 (7) ◽  
pp. 1919-1928 ◽  
Author(s):  
Jacob Romano ◽  
Guy Nimrod ◽  
Nir Ben-Tal ◽  
Yona Shadkchan ◽  
Koti Baruch ◽  
...  

The ECM33/SPS2 family of glycosylphosphatidylinositol-anchored proteins plays an important role in maintaining fungal cell wall integrity and virulence. However, the precise molecular role of these proteins is unknown. In this work, AfuEcm33, the gene encoding the ECM33 homologue in the important pathogenic fungus Aspergillus fumigatus, has been cloned and its function analysed. It is shown that disruption of AfuEcm33 results in rapid conidial germination, increased cell–cell adhesion, resistance to the antifungal agent caspofungin and increased virulence in an immunocompromised mouse model for disseminated aspergillosis. These results suggest that the protein encoded by AfuEcm33 is involved in key aspects of cell wall morphogenesis and plays an important role in A. fumigatus virulence.


Author(s):  
Yuanwei Zhang ◽  
Wenxia Fang ◽  
Olawale G. Raimi ◽  
Deborah E. A. Lockhart ◽  
Andrew T. Ferenbach ◽  
...  

2000 ◽  
Vol 20 (1) ◽  
pp. 12-25 ◽  
Author(s):  
Hsin-Yao Tang ◽  
Jing Xu ◽  
Mingjie Cai

ABSTRACT The EH domain proteins Pan1p and End3p of budding yeast have been known to form a complex in vivo and play important roles in organization of the actin cytoskeleton and endocytosis. In this report, we describe new findings concerning the function of the Pan1p-End3p complex. First, we found that the Pan1p-End3p complex associates with Sla1p, another protein known to be required for the assembly of cortical actin structures. Sla1p interacts with the first long repeat region of Pan1p and the N-terminal EH domain of End3p, thus leaving the Pan1p-End3p interaction, which requires the second long repeat of Pan1p and the C-terminal repeat region of End3p, undisturbed. Second, Pan1p, End3p, and Sla1p are also required for normal cell wall morphogenesis. Each of the Pan1-4, sla1Δ, andend3Δ mutants displays the abnormal cell wall morphology previously reported for the act1-1 mutant. These cell wall defects are also exhibited by wild-type cells overproducing the C-terminal region of Sla1p that is responsible for interactions with Pan1p and End3p. These results indicate that the functions of Pan1p, End3p, and Sla1p in cell wall morphogenesis may depend on the formation of a heterotrimeric complex. Interestingly, the cell wall abnormalities exhibited by these cells are independent of the actin cytoskeleton organization on the cell cortex, as they manifest despite the presence of apparently normal cortical actin cytoskeleton. Examination of several act1 mutants also supports this conclusion. These observations suggest that the Pan1p-End3p-Sla1p complex is required not only for normal actin cytoskeleton organization but also for normal cell wall morphogenesis in yeast.


2008 ◽  
Vol 45 (3) ◽  
pp. 232-242 ◽  
Author(s):  
Ravit Belaish ◽  
Haim Sharon ◽  
Emma Levdansky ◽  
Shulamit Greenstein ◽  
Yana Shadkchan ◽  
...  

PLoS Genetics ◽  
2019 ◽  
Vol 15 (12) ◽  
pp. e1008551 ◽  
Author(s):  
Patrícia Alves de Castro ◽  
Ana Cristina Colabardini ◽  
Adriana Oliveira Manfiolli ◽  
Jéssica Chiaratto ◽  
Lilian Pereira Silva ◽  
...  

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