scholarly journals Characterization of the Aspergillus fumigatus phosphomannose isomerase Pmi1 and its impact on cell wall synthesis and morphogenesis

Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3281-3293 ◽  
Author(s):  
Wenxia Fang ◽  
Xiaoying Yu ◽  
Bin Wang ◽  
Hui Zhou ◽  
Haomiao Ouyang ◽  
...  

Phosphomannose isomerase (PMI) is an enzyme catalysing the interconversion of mannose 6-phosphate (Man-6-P) and fructose 6-phosphate (Fru-6-P). The reaction catalysed by PMI is the first committed step in the synthesis of mannose-containing sugar chains and provides a link between glucose metabolism and mannosylation. In this study, the pmi1 gene was identified to encode PMI in the human fungal pathogen Aspergillus fumigatus. Characterization of A. fumigatus Pmi1 expressed in Escherichia coli revealed that this PMI mainly catalysed the conversion of Fru-6-P to Man-6-P and that its binding affinity for Man-6-P was similar to that of yeast PMIs, but different to those of PMIs from bacteria or animals. Loss of pmi1 was lethal unless Man was provided in the growth medium. However, a Δpmi1 mutant cell showed a significantly reduced growth rate at a high concentration of Man. Biochemical analysis revealed that both inadequate and replete Man led to an accumulation of intracellular Man-6-P and a reduction in the amount of α-glucan in the cell wall. Uncoupling of the link between energy production and glycosylation by deletion of the pmi1 gene led to phenotypes such as defects in cell wall integrity, abnormal morphology and reduced conidiation. Our results reveal that PMI activity is essential for viability and plays a central regulatory role in both cell wall synthesis and energy production in A. fumigatus.

2012 ◽  
Vol 57 (1) ◽  
pp. 626-628 ◽  
Author(s):  
Susanne Perkhofer ◽  
Barbara Striessnig ◽  
Bettina Sartori ◽  
Barbara Hausott ◽  
Helmut W. Ott ◽  
...  

ABSTRACTThe combination of platelets and anidulafungin at 0.03 μg/ml significantly (P< 0.05) reduced the germination rate and hyphal elongation inAspergillus fumigatuscompared to those with either anidulafungin only or an untreated control. Platelets decreased the expression of thefksgene, which plays an important role in cell wall synthesis. Our results suggest that human platelets plus anidulafungin might contribute to defense againstA. fumigatus.


1999 ◽  
Vol 262 (2) ◽  
pp. 368-374 ◽  
Author(s):  
Kazuo Omi ◽  
Hikaru Sonoda ◽  
Kiyoshi Nagata ◽  
Kenji Sugita

2013 ◽  
Vol 289 (3) ◽  
pp. 1243-1256 ◽  
Author(s):  
Mark J. Lee ◽  
Fabrice N. Gravelat ◽  
Robert P. Cerone ◽  
Stefanie D. Baptista ◽  
Paolo V. Campoli ◽  
...  

The cell wall of Aspergillus fumigatus contains two galactose-containing polysaccharides, galactomannan and galactosaminogalactan, whose biosynthetic pathways are not well understood. The A. fumigatus genome contains three genes encoding putative UDP-glucose 4-epimerases, uge3, uge4, and uge5. We undertook this study to elucidate the function of these epimerases. We found that uge4 is minimally expressed and is not required for the synthesis of galactose-containing exopolysaccharides or galactose metabolism. Uge5 is the dominant UDP-glucose 4-epimerase in A. fumigatus and is essential for normal growth in galactose-based medium. Uge5 is required for synthesis of the galactofuranose (Galf) component of galactomannan and contributes galactose to the synthesis of galactosaminogalactan. Uge3 can mediate production of both UDP-galactose and UDP-N-acetylgalactosamine (GalNAc) and is required for the production of galactosaminogalactan but not galactomannan. In the absence of Uge5, Uge3 activity is sufficient for growth on galactose and the synthesis of galactosaminogalactan containing lower levels of galactose but not the synthesis of Galf. A double deletion of uge5 and uge3 blocked growth on galactose and synthesis of both Galf and galactosaminogalactan. This study is the first survey of glucose epimerases in A. fumigatus and contributes to our understanding of the role of these enzymes in metabolism and cell wall synthesis.


2002 ◽  
Vol 40 (5) ◽  
pp. 455-464 ◽  
Author(s):  
I. Mouyna ◽  
J. Sarfati ◽  
P. Recco ◽  
T. Fontaine ◽  
B. Henrissat ◽  
...  

2007 ◽  
Vol 6 (12) ◽  
pp. 2260-2268 ◽  
Author(s):  
Hui Zhou ◽  
Hongyan Hu ◽  
Lijuan Zhang ◽  
Ruoyu Li ◽  
Haomiao Ouyang ◽  
...  

ABSTRACT Protein O-mannosyltransferases initiate O mannosylation of secretory proteins, which are of fundamental importance in eukaryotes. In this study, the PMT gene family of the human fungal pathogen Aspergillus fumigatus was identified and characterized. Unlike the case in Saccharomyces cerevisiae, where the PMT family is highly redundant, only one member of each PMT subfamily, namely, Afpmt1, Afpmt2, and Afpmt4, is present in A. fumigatus. Mutants with a deletion of Afpmt1 are viable. In vitro and in vivo activity assays confirmed that the protein encoded by Afpmt1 acts as an O-mannosyltransferase (AfPmt1p). Characterization of the ΔAfpmt1 mutant showed that a lack of AfPmt1p results in sensitivity to elevated temperature and defects in growth and cell wall integrity, thereby affecting cell morphology, conidium formation, and germination. In a mouse model, Afpmt1 was not required for the virulence of A. fumigatus under the experimental conditions used.


Biochemistry ◽  
2002 ◽  
Vol 41 (43) ◽  
pp. 13053-13058 ◽  
Author(s):  
Lynette Cegelski ◽  
Sung Joon Kim ◽  
Andrew W. Hing ◽  
Daniel R. Studelska ◽  
Robert D. O'Connor ◽  
...  

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