scholarly journals A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata

2007 ◽  
Vol 104 (18) ◽  
pp. 7628-7633 ◽  
Author(s):  
Rupinder Kaur ◽  
Biao Ma ◽  
Brendan P. Cormack

Candida glabrata is a yeast pathogen of humans. We have established a tissue culture model to analyze the interaction of C. glabrata with macrophages. Transcript profiling of yeast ingested by macrophages reveals global changes in metabolism as well as increased expression of a gene family (YPS genes) encoding extracellular glycosylphosphatidylinositol-linked aspartyl proteases. Eight of these YPS genes are found in a cluster that is unique to C. glabrata. Genetic analysis shows that the C. glabrata YPS genes are required for cell wall integrity, adherence to mammalian cells, survival in macrophages and virulence. By monitoring the processing of a cell wall adhesin, Epa1, we also show that Yps proteases play an important role in cell wall re-modeling by removal and release of glycosylphosphatidylinositol-anchored cell wall proteins.

2021 ◽  
Vol 9 (6) ◽  
pp. 1323
Author(s):  
Etai Boichis ◽  
Nadejda Sigal ◽  
Ilya Borovok ◽  
Anat A. Herskovits

Infection of mammalian cells by Listeria monocytogenes (Lm) was shown to be facilitated by its phage elements. In a search for additional phage remnants that play a role in Lm’s lifecycle, we identified a conserved locus containing two XRE regulators and a pair of genes encoding a secreted metzincin protease and a lipoprotein structurally similar to a TIMP-family metzincin inhibitor. We found that the XRE regulators act as a classic CI/Cro regulatory switch that regulates the expression of the metzincin and TIMP-like genes under intracellular growth conditions. We established that when these genes are expressed, their products alter Lm morphology and increase its sensitivity to phage mediated lysis, thereby enhancing virion release. Expression of these proteins also sensitized the bacteria to cell wall targeting compounds, implying that they modulate the cell wall structure. Our data indicate that these effects are mediated by the cleavage of the TIMP-like protein by the metzincin, and its subsequent release to the extracellular milieu. While the importance of this locus to Lm pathogenicity remains unclear, the observation that this phage-associated protein pair act upon the bacterial cell wall may hold promise in the field of antibiotic potentiation to combat antibiotic resistant bacterial pathogens.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Bai-Ling Chen ◽  
Wuttichai Mhuantong ◽  
Shih-Hsin Ho ◽  
Jo-Shu Chang ◽  
Xin-Qing Zhao ◽  
...  

Abstract Background Scenedesmus obliquus belongs to green microalgae and is widely used in aquaculture as feed, which is also explored for lipid production and bioremediation. However, genomic studies of this microalga have been very limited. Cell self-flocculation of microalgal cells can be used as a simple and economic method for harvesting biomass, and it is of great importance to perform genome-scale studies for the self-flocculating S. obliquus strains to promote their biotechnological applications. Results We employed the Pacific Biosciences sequencing platform for sequencing the genome of the self-flocculating microalga S. obliquus AS-6-11, and used the MECAT software for de novo genome assembly. The estimated genome size of S. obliquus AS-6-11 is 172.3 Mbp with an N50 of 94,410 bp, and 31,964 protein-coding genes were identified. Gene Ontology (GO) and KEGG pathway analyses revealed 65 GO terms and 428 biosynthetic pathways. Comparing to the genome sequences of the well-studied green microalgae Chlamydomonas reinhardtii, Chlorella variabilis, Volvox carteri and Micractinium conductrix, the genome of S. obliquus AS-6-11 encodes more unique proteins, including one gene that encodes D-mannose binding lectin. Genes encoding the glycosylphosphatidylinositol (GPI)-anchored cell wall proteins, and proteins with fasciclin domains that are commonly found in cell wall proteins might be responsible for the self-flocculating phenotype, and were analyzed in detail. Four genes encoding both GPI-anchored cell wall proteins and fasciclin domain proteins are the most interesting targets for further studies. Conclusions The genome sequence of the self-flocculating microalgal S. obliquus AS-6-11 was annotated and analyzed. To our best knowledge, this is the first report on the in-depth annotation of the S. obliquus genome, and the results will facilitate functional genomic studies and metabolic engineering of this important microalga. The comparative genomic analysis here also provides new insights into the evolution of green microalgae. Furthermore, identification of the potential genes encoding self-flocculating proteins will benefit studies on the molecular mechanism underlying this phenotype for its better control and biotechnological applications as well.


Microbiology ◽  
2007 ◽  
Vol 153 (7) ◽  
pp. 2137-2147 ◽  
Author(s):  
Artemio Mendoza-Mendoza ◽  
Teresa. Rosales-Saavedra ◽  
Carlos. Cortés ◽  
Verónica. Castellanos-Juárez ◽  
Pedro. Martínez ◽  
...  

2002 ◽  
Vol 184 (7) ◽  
pp. 2058-2061 ◽  
Author(s):  
Mark D. McNemar ◽  
William A. Fonzi

ABSTRACT The opportunistic fungal pathogen, Candida albicans, is reported to have several potential virulence factors. A potentially significant factor is the ability to undergo morphological transition from yeast to hypha. This alteration of form is accompanied by many changes within the cell, including alterations in gene expression and cell wall composition. We have isolated a gene that encodes a highly conserved serine/threonine kinase that appears to be involved in the regulation of proteins associated with the cell wall. We have assigned the designation CBK1 (cell wall biosynthesis kinase 1) to this gene. Mutants lacking CBK1 form large aggregates of round cells under all growth conditions and lack the ability to undergo morphological differentiation. Additionally, these mutants show an altered pattern of expression of several transcripts encoding proteins associated with the cell wall. The results suggest that the kinase encoded by CBK1 plays a general role in the maintenance and alteration of the cell wall of C. albicans in all morphologies.


2005 ◽  
Vol 73 (6) ◽  
pp. 3773-3777 ◽  
Author(s):  
Céline M. Lévesque ◽  
Elena Voronejskaia ◽  
Yi-Chen Cathy Huang ◽  
Richard W. Mair ◽  
Richard P. Ellen ◽  
...  

ABSTRACT Streptococcus mutans is one of the best-known biofilm-forming organisms associated with humans. We investigated the role of the sortase gene (srtA) in monospecies biofilm formation and observed that inactivation of srtA caused a decrease in biofilm formation. Genes encoding three putative sortase-dependent proteins were also found to be up-regulated in biofilms versus planktonic cells and mutations in these genes resulted in reduced biofilm biomass.


2010 ◽  
Vol 54 (4) ◽  
pp. 1639-1643 ◽  
Author(s):  
Taiga Miyazaki ◽  
Shunsuke Yamauchi ◽  
Tatsuo Inamine ◽  
Yosuke Nagayoshi ◽  
Tomomi Saijo ◽  
...  

ABSTRACT A Candida glabrata calcineurin mutant exhibited increased susceptibility to both azole antifungal and cell wall-damaging agents and was also attenuated in virulence. Although a mutant lacking the downstream transcription factor Crz1 displayed a cell wall-associated phenotype intermediate to that of the calcineurin mutant and was modestly attenuated in virulence, it did not show increased azole susceptibility. These results suggest that calcineurin regulates both Crz1-dependent and -independent pathways depending on the type of stress.


2020 ◽  
Author(s):  
Bailing Chen ◽  
Wuttichai Mhuantong ◽  
Shih-Hsin Ho ◽  
Jo-Shu Chang ◽  
Xinqing Zhao ◽  
...  

Abstract Background: Scenedesmus obliquus belongs to green microalgae and is widely used in aquaculture as feed, which is also explored for lipid production and bioremediation. However, genomic studies of this microalga have been very limited. Cell self-flocculation of microalgal cells can be used as a simple and economic method for harvesting biomass, and it is of great importance to perform genome-scale studies for the self-flocculating S. obliquus strains to promote their biotechnological applications.Results: We employed the Pacific Biosciences sequencing platform for sequencing the genome of the self-flocculat ing microalga S. obliquus AS-6-11, and used the MECAT software for de novo genome assembly. The estimated genome size of S. obliquus AS-6-11 is 172.3 Mbp with an N50 of 94,410 bp, and 31,964 protein-coding genes were identified. Gene Ontology (GO) and KEGG pathway analyses revealed 65 GO terms and 428 biosynthetic pathways. Comparing to the genome sequences of the well-studied green microalgae Chlamydomonas reinhardtii, Chlorella variabilis, Volvox carteri and Micractinium conductrix, the genome of S. obliquus AS-6-11 encodes more unique proteins, including one gene that encodes D-mannose binding lectin. Genes encoding the glycosylphosphatidylinositol (GPI)-anchored cell wall proteins, and proteins with fasciclin domains that are commonly found in cell wall proteins might be responsible for the self-flocculating phenotype, and were analyzed in detail. Four genes encoding both GPI-anchored cell wall proteins and fasciclin domain proteins are the most interesting targets for further studies.Conclusions: To our best knowledge, this is the first report on the in-depth annotation of the S. obliquus genome, and the results will facilitate functional genomic studies and metabolic engineering of this important microalga. The comparative genomic analysis here also provides new insights into the evolution of green microalgae. Furthermore, identification of the potential genes encoding self-flocculating proteins will benefit studies on the molecular mechanism underlying this phenotype for its better control and biotechnological applications as well.


2020 ◽  
Author(s):  
Bailing Chen ◽  
Wuttichai Mhuantong ◽  
Shih-Hsin Ho ◽  
Jo-Shu Chang ◽  
Xinqing Zhao ◽  
...  

Abstract Background: Scenedesmus obliquus belongs to green microalgae and is widely used in aquaculture as feed, which is also explored for lipid production and bioremediation. However, genomic studies of this microalga have been very limited. Cell self-flocculation of microalgal cells can be used as a simple and economic method for harvesting biomass, and it is of great importance to perform genome-scale studies for the self-flocculating S. obliquus strains to promote their biotechnological applications.Results: We employed the Pacific Biosciences sequencing platform for sequencing the genome of the self-flocculating microalga S. obliquus AS-6-11, and used the MECAT software for de novo genome assembly. The estimated genome size of S. obliquus AS-6-11 is 172.3 Mbp with an N50 of 94,410 bp, and 31,964 protein-coding genes were identified. Gene Ontology (GO) and KEGG pathway analyses revealed 65 GO terms and 428 biosynthetic pathways. Comparing to the genome sequences of the well-studied green microalgae Chlamydomonas reinhardtii, Chlorella variabilis, Volvox carteri and Micractinium conductrix, the genome of S. obliquus AS-6-11 encodes more unique proteins, including one gene that encodes D-mannose binding lectin. Genes encoding the glycosylphosphatidylinositol (GPI)-anchored cell wall proteins, and proteins with fasciclin domains that are commonly found in cell wall proteins might be responsible for the self-flocculating phenotype, and were analyzed in detail. Four genes encoding both GPI-anchored cell wall proteins and fasciclin domain proteins are the most interesting targets for further studies.Conclusions: To our best knowledge, this is the first report on the in-depth annotation of the S. obliquus genome, and the results will facilitate functional genomic studies and metabolic engineering of this important microalga. The comparative genomic analysis here also provides new insights into the evolution of green microalgae. Furthermore, identification of the potential genes encoding self-flocculating proteins will benefit studies on the molecular mechanism underlying this phenotype for its better control and biotechnological applications as well.


2002 ◽  
Vol 115 (12) ◽  
pp. 2549-2558 ◽  
Author(s):  
Jose M. Rodriguez-Peña ◽  
Cristina Rodriguez ◽  
Alberto Alvarez ◽  
César Nombela ◽  
Javier Arroyo

The cell wall is an essential structure that preserves the osmotic integrity of fungal cells and determines cellular morphology during developmental programs. The high number of different wall components demands a variety of processes to deliver precursors and synthetic proteins to the proper location at the right time for wall development and modification. Here,the specificity of the mechanisms that regulate the temporal and spatial localisation of cell wall proteins to sites of polarised growth in Saccharomyces cerevisiae is investigated. For this purpose, the localisation of Crh2p, a cell wall glycosylphosphatidylinositol (GPI)-anchored mannoprotein that we have recently described as involved in cell wall construction and localised to polarised growth sites, was followed using a Crh2p-GFP fusion protein. Crh2p distribution was studied in several genetic backgrounds affected in different steps of the cell polarity establishment machinery or/and bud morphogenesis. Crh2p is localised at the mother-bud neck in bud1 cells following the random budding pattern characteristic of this mutant. The Crh2p distribution was greatly altered in a cdc42-1mutant, indicating complete dependence on an organised actin cytoskeleton for polarised Crh2p distribution. The usual deposition of Crh2p in a ring at the base of growing buds was lacking in cdc10-11 cells growing under restrictive temperature conditions, whereas Crh2p deposition at the septum region was absent in both cdc10-11 and cdc15-lyt1 cells. These results point to the dependence of Crh2p localisation at the bud-neck on both septins and septum integrity. Furthermore, in the absence of Bni4p, a scaffold protein involved in the targeting of the chitin synthase III complex to the bud neck, Crh2p was not longer found at the neck in large-budded cells undergoing cytokinesis. Finally, Crh2p was not properly localised in cells deleted in CHS5, which encodes a protein involved in the transport of Chs3p, and was completely mislocalised in sbe2/sbe22 mutants,suggesting that the transport systems for Chs3p and Crh2p are to a certain extent coincident. The transport of other GPI-cell wall proteins, such as Cwp1p, however, does not depend on these systems as the localisation of the latter protein was not affected in either of these mutants.


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