scholarly journals A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation

PLoS Genetics ◽  
2021 ◽  
Vol 17 (10) ◽  
pp. e1009817
Author(s):  
Pengjie Hu ◽  
Hao Ding ◽  
Lan Shen ◽  
Guang-Jun He ◽  
Huimin Liu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cellular Response ◽  
Surface Protein ◽  
Pathogenic Fungi ◽  
Phenotypic Analysis ◽  
Critical Determinant ◽  
Signal Specificity ◽  
Dependent Cell ◽  
Atp Supply ◽  
Unique Cell

The yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans, which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distinct stimuli: mating stimulation or glucosamine (GlcN), the monomer of cell wall chitosan. However, it remains poorly understood how the signal specificity for Cryptococcus morphological transition by disparate stimuli is ensured. Here, by integrating temporal expression signature analysis and phenome-based clustering evaluation, we demonstrate that GlcN specifically triggers a unique cellular response, which acts as a critical determinant underlying the activation of GlcN-induced filamentation (GIF). This cellular response is defined by an unusually hyperactive cell wall synthesis that is highly ATP-consuming. A novel cell surface protein Gis1 was identified as the indicator molecule for the GlcN-induced cell wall response. The Mpk1-directed cell wall pathway critically bridges global cell wall gene induction and intracellular ATP supply, ensuring the Gis1-dependent cell wall response and the stimulus specificity of GIF. We further reveal that the ability of Mpk1 to coordinate the cell wall response and GIF activation is conserved in different Cryptococcus pathogens. Phosphoproteomics-based profiling together with genetic and phenotypic analysis revealed that the Mpk1 kinase mediates the regulatory specificity of GIF through a coordinated downstream regulatory network centered on Skn7 and Crz1. Overall, our findings discover an unprecedented and conserved cell wall biosynthesis-dependent fungal differentiation commitment mechanism, which enables the signal specificity of pathogenicity-related dimorphism induced by GlcN in Cryptococcus pathogens.

The Regulatory Function of the Molecular Chaperone Hsp90 in the Cell Wall Integrity of Pathogenic Fungi

2018 ◽  
Vol 16 (1) ◽  
pp. 44-53
Author(s):  
Marina Campos Rocha ◽  
Camilla Alves Santos ◽  
Iran Malavazi
Keyword(s):  
Cell Wall ◽  
Antifungal Therapy ◽  
Molecular Chaperone ◽  
Regulatory Protein ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Cell Wall Integrity ◽  
Regulatory Function ◽  
Loss Of Function ◽  
Hsp90 Inhibition

Different signaling cascades including the Cell Wall Integrity (CWI), the High Osmolarity Glycerol (HOG) and the Ca2+/calcineurin pathways control the cell wall biosynthesis and remodeling in fungi. Pathogenic fungi, such as Aspergillus fumigatus and Candida albicans, greatly rely on these signaling circuits to cope with different sources of stress, including the cell wall stress evoked by antifungal drugs and the host’s response during infection. Hsp90 has been proposed as an important regulatory protein and an attractive target for antifungal therapy since it stabilizes major effector proteins that act in the CWI, HOG and Ca2+/calcineurin pathways. Data from the human pathogen C. albicans have provided solid evidence that loss-of-function of Hsp90 impairs the evolution of resistance to azoles and echinocandin drugs. In A. fumigatus, Hsp90 is also required for cell wall integrity maintenance, reinforcing a coordinated function of the CWI pathway and this essential molecular chaperone. In this review, we focus on the current information about how Hsp90 impacts the aforementioned signaling pathways and consequently the homeostasis and maintenance of the cell wall, highlighting this cellular event as a key mechanism underlying antifungal therapy based on Hsp90 inhibition.

scholarly journals Identification and Characterization of a Peptidoglycan Hydrolase, MurA, of Listeria monocytogenes, a Muramidase Needed for Cell Separation

2003 ◽  
Vol 185 (23) ◽  
pp. 6801-6808 ◽  
Author(s):  
Shannon A. Carroll ◽  
Torsten Hain ◽  
Ulrike Technow ◽  
Ayub Darji ◽  
Philippos Pashalidis ◽  
...  
Keyword(s):  
Cell Wall ◽  
Listeria Monocytogenes ◽  
Cell Separation ◽  
Bacterial Species ◽  
Surface Protein ◽  
Wild Type ◽  
Terminal Domain ◽  
Cell Wall Hydrolase ◽  
Characteristic Features ◽  
Type Gene

ABSTRACT A novel cell wall hydrolase encoded by the murA gene of Listeria monocytogenes is reported here. Mature MurA is a 66-kDa cell surface protein that is recognized by the well-characterized L. monocytogenes-specific monoclonal antibody EM-7G1. MurA displays two characteristic features: (i) an N-terminal domain with homology to muramidases from several gram-positive bacterial species and (ii) four copies of a cell wall-anchoring LysM repeat motif present within its C-terminal domain. Purified recombinant MurA produced in Escherichia coli was confirmed to be an authentic cell wall hydrolase with lytic properties toward cell wall preparations of Micrococcus lysodeikticus. An isogenic mutant with a deletion of murA that lacked the 66-kDa cell wall hydrolase grew as long chains during exponential growth. Complementation of the mutant strain by chromosomal reintegration of the wild-type gene restored expression of this murein hydrolase activity and cell separation levels to those of the wild-type strain. Studies reported herein suggest that the MurA protein is involved in generalized autolysis of L. monocytogenes.

PMR4-dependent cell wall depositions are a consequence but not the cause of temperature-induced autoimmunity

2021 ◽  
Author(s):  
Giuliana Hessler ◽  
Stephan Michael Portheine ◽  
Eva-Maria Gerlach ◽  
Tim Lienemann ◽  
Gerald Koch ◽  
...  
Keyword(s):  
Cell Wall ◽  
Immune System ◽  
Severe Damage ◽  
Temperature Dependent ◽  
Callose Synthase ◽  
Ambient Temperatures ◽  
Point Of No Return ◽  
Dependent Cell ◽  
And Function ◽  
Reduced Temperature

Abstract Plants possess a well-balanced immune system that is required for defense against pathogen infections. In autoimmune mutants or necrotic crosses, an intrinsic temperature-dependent imbalance leads to constitutive immune activation, resulting in severe damage or even death of plants. Recently, cell wall depositions were described as one of the symptoms following induction of the autoimmune phenotype in Arabidopsis saul1-1 mutants. However, the regulation and function of these depositions remained unclear. Here, we show that cell wall depositions, containing lignin and callose, were a common autoimmune feature and were deposited in proportion to the severity of the autoimmune phenotype at reduced ambient temperatures. When plants were exposed to reduced temperature for periods insufficient to induce an autoimmune phenotype, the cell wall depositions were not present. After low temperature intervals, sufficient to induce autoimmune responses, cell wall depositions correlated with a point of no return in saul1-1 autoimmunity. Although cell wall depositions were largely abolished in saul1-1 pmr4-1 double mutants lacking SAUL1 and the callose synthase gene GSL5/PMR4, their phenotype remained unchanged compared to that of the saul1-1 single mutant. Our data showed that cell wall depositions generally occur in autoimmunity, but appear not to be the cause of autoimmune phenotypes.

scholarly journals The Role of Arabinogalactan Type II Degradation in Plant-Microbe Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Guadalupe Villa-Rivera ◽  
Horacio Cano-Camacho ◽  
Everardo López-Romero ◽  
María Guadalupe Zavala-Páramo
Keyword(s):  
Cell Wall ◽  
Plant Defense ◽  
Plant Cell ◽  
Plant Cell Wall ◽  
Degradation Products ◽  
Hydrolytic Enzymes ◽  
Pathogenic Fungi ◽  
Plant Interactions ◽  
Root Tips ◽  
Microbe Interactions

Arabinogalactans (AGs) are structural polysaccharides of the plant cell wall. A small proportion of the AGs are associated with hemicellulose and pectin. Furthermore, AGs are associated with proteins forming the so-called arabinogalactan proteins (AGPs), which can be found in the plant cell wall or attached through a glycosylphosphatidylinositol (GPI) anchor to the plasma membrane. AGPs are a family of highly glycosylated proteins grouped with cell wall proteins rich in hydroxyproline. These glycoproteins have important and diverse functions in plants, such as growth, cellular differentiation, signaling, and microbe-plant interactions, and several reports suggest that carbohydrate components are crucial for AGP functions. In beneficial plant-microbe interactions, AGPs attract symbiotic species of fungi or bacteria, promote the development of infectious structures and the colonization of root tips, and furthermore, these interactions can activate plant defense mechanisms. On the other hand, plants secrete and accumulate AGPs at infection sites, creating cross-links with pectin. As part of the plant cell wall degradation machinery, beneficial and pathogenic fungi and bacteria can produce the enzymes necessary for the complete depolymerization of AGs including endo-β-(1,3), β-(1,4) and β-(1,6)-galactanases, β-(1,3/1,6) galactanases, α-L-arabinofuranosidases, β-L-arabinopyranosidases, and β-D-glucuronidases. These hydrolytic enzymes are secreted during plant-pathogen interactions and could have implications for the function of AGPs. It has been proposed that AGPs could prevent infection by pathogenic microorganisms because their degradation products generated by hydrolytic enzymes of pathogens function as damage-associated molecular patterns (DAMPs) eliciting the plant defense response. In this review, we describe the structure and function of AGs and AGPs as components of the plant cell wall. Additionally, we describe the set of enzymes secreted by microorganisms to degrade AGs from AGPs and its possible implication for plant-microbe interactions.

Transcriptome profiling of aSaccharomyces cerevisiaemutant with a constitutively activated Ras/cAMP pathway

2003 ◽  
Vol 16 (1) ◽  
pp. 107-118 ◽  
Author(s):  
D. L. Jones ◽  
J. Petty ◽  
D. C. Hoyle ◽  
A. Hayes ◽  
E. Ragni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Wall ◽  
Microarray Analysis ◽  
Cellular Response ◽  
Ribosome Biogenesis ◽  
Biological Significance ◽  
Altered Expression ◽  
Wall Functions ◽  
Constitutive Activation ◽  
Camp Pathway

Often changes in gene expression levels have been considered significant only when above/below some arbitrarily chosen threshold. We investigated the effect of applying a purely statistical approach to microarray analysis and demonstrated that small changes in gene expression have biological significance. Whole genome microarray analysis of a pde2Δ mutant, constructed in the Saccharomyces cerevisiae reference strain FY23, revealed altered expression of ∼11% of protein encoding genes. The mutant, characterized by constitutive activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced ability to assimilate nonfermentable carbon sources, and some cell wall integrity defects. Applying the Munich Information Centre for Protein Sequences (MIPS) functional categories revealed increased expression of genes related to ribosome biogenesis and downregulation of genes in the cell rescue, defense, cell death and aging category, suggesting a decreased response to stress conditions. A reduced level of gene expression in the unfolded protein response pathway (UPR) was observed. Cell wall genes whose expression was affected by this mutation were also identified. Several of the cAMP-responsive orphan genes, upon further investigation, revealed cell wall functions; others had previously unidentified phenotypes assigned to them. This investigation provides a statistical global transcriptome analysis of the cellular response to constitutive activation of the Ras/cAMP pathway.

scholarly journals Induction of Fusarium lytic Enzymes by Extracts from Resistant and Susceptible Cultivars of Pea (Pisum sativum L.)

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 976
Author(s):  
Lakshmipriya Perincherry ◽  
Chaima Ajmi ◽  
Souheib Oueslati ◽  
Agnieszka Waśkiewicz ◽  
Łukasz Stępień
Keyword(s):  
Cell Wall ◽  
Plant Extracts ◽  
Plant Cell Wall ◽  
Pathogenic Fungi ◽  
Human Beings ◽  
Cell Wall Degrading Enzymes ◽  
Lytic Enzymes ◽  
Mycelium Growth ◽  
Oat Bran

Being pathogenic fungi, Fusarium produce various extracellular cell wall-degrading enzymes (CWDEs) that degrade the polysaccharides in the plant cell wall. They also produce mycotoxins that contaminate grains, thereby posing a serious threat to animals and human beings. Exposure to mycotoxins occurs through ingestion of contaminated grains, inhalation and through skin absorption, thereby causing mycotoxicoses. The toxins weaken the host plant, allowing the pathogen to invade successfully, with the efficiency varying from strain to strain and depending on the plant infected. Fusariumoxysporum predominantly produces moniliformin and cyclodepsipeptides, whereas F. proliferatum produces fumonisins. The aim of the study was to understand the role of various substrates and pea plant extracts in inducing the production of CWDEs and mycotoxins. Additionally, to monitor the differences in their levels when susceptible and resistant pea plant extracts were supplemented. The cultures of F. proliferatum and F. oxysporum strains were supplemented with various potential inducers of CWDEs. During the initial days after the addition of substrates, the fungus cocultivated with pea extracts and other carbon substrates showed increased activities of β-glucosidase, xylanase, exo-1,4-glucanase and lipase. The highest inhibition of mycelium growth (57%) was found in the cultures of F. proliferatum strain PEA1 upon the addition of cv. Sokolik extract. The lowest fumonisin content was exhibited by the cultures with the pea extracts and oat bran added, and this can be related to the secondary metabolites and antioxidants present in these substrates.

scholarly journals Cellulose synthase interactive1- and microtubule-dependent cell wall architecture is required for acid growth in Arabidopsis hypocotyls

2020 ◽  
Vol 71 (10) ◽  
pp. 2982-2994 ◽  
Author(s):  
Xiaoran Xin ◽  
Lei Lei ◽  
Yunzhen Zheng ◽  
Tian Zhang ◽  
Sai Venkatesh Pingali ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Elongation ◽  
Plant Cell Wall ◽  
Cellulose Microfibrils ◽  
Crystalline Cellulose ◽  
Cellulose Content ◽  
Acid Growth ◽  
Cell Wall Assembly ◽  
Dependent Cell ◽  
Cell Wall Architecture

Abstract Auxin-induced cell elongation relies in part on the acidification of the cell wall, a process known as acid growth that presumably triggers expansin-mediated wall loosening via altered interactions between cellulose microfibrils. Cellulose microfibrils are a major determinant for anisotropic growth and they provide the scaffold for cell wall assembly. Little is known about how acid growth depends on cell wall architecture. To explore the relationship between acid growth-mediated cell elongation and plant cell wall architecture, two mutants (jia1-1 and csi1-3) that are defective in cellulose biosynthesis and cellulose microfibril organization were analyzed. The study revealed that cell elongation is dependent on CSI1-mediated cell wall architecture but not on the overall crystalline cellulose content. We observed a correlation between loss of crossed-polylamellate walls and loss of auxin- and fusicoccin-induced cell growth in csi1-3. Furthermore, induced loss of crossed-polylamellate walls via disruption of cortical microtubules mimics the effect of csi1 in acid growth. We hypothesize that CSI1- and microtubule-dependent crossed-polylamellate walls are required for acid growth in Arabidopsis hypocotyls.

scholarly journals The Cell Wall Lipid PDIM Contributes to Phagosomal Escape and Host Cell Exit of Mycobacterium tuberculosis

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Jeff Quigley ◽  
V. Keith Hughitt ◽  
Carlos A. Velikovsky ◽  
Roy A. Mariuzza ◽  
Najib M. El-Sayed ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Transcriptional Repressor ◽  
Cell Manipulation ◽  
Human Pathogen ◽  
Cell Necrosis ◽  
Unique Cell ◽  
Intracellular Vacuole

ABSTRACT The cell wall of Mycobacterium tuberculosis is composed of unique lipids that are important for pathogenesis. Indeed, the first-ever genetic screen in M. tuberculosis identified genes involved in the biosynthesis and transport of the cell wall lipid PDIM (phthiocerol dimycocerosates) as crucial for the survival of M. tuberculosis in mice. Here we show evidence for a novel molecular mechanism of the PDIM-mediated virulence in M. tuberculosis. We characterized the DNA interaction and the regulon of Rv3167c, a transcriptional repressor that is involved in virulence regulation of M. tuberculosis, and discovered that it controls the PDIM operon. A loss-of-function genetic approach showed that PDIM levels directly correlate with the capacity of M. tuberculosis to escape the phagosome and induce host cell necrosis and macroautophagy. In conclusion, our study attributes a novel role of the cell wall lipid PDIM in intracellular host cell modulation, which is important for host cell exit and dissemination of M. tuberculosis. IMPORTANCE Mycobacterium tuberculosis is a major human pathogen that has coevolved with its host for thousands of years. The complex and unique cell wall of M. tuberculosis contains the lipid PDIM (phthiocerol dimycocerosates), which is crucial for virulence of the bacterium, but its function is not well understood. Here we show that PDIM expression by M. tuberculosis is negatively regulated by a novel transcriptional repressor, Rv3167c. In addition, we discovered that the escape of M. tuberculosis from its intracellular vacuole was greatly augmented by the presence of PDIM. The increased release of M. tuberculosis into the cytosol led to increased host cell necrosis. The discovery of a link between the cell wall lipid PDIM and a major pathogenesis pathway of M. tuberculosis provides important insights into the molecular mechanisms of host cell manipulation by M. tuberculosis. IMPORTANCE Mycobacterium tuberculosis is a major human pathogen that has coevolved with its host for thousands of years. The complex and unique cell wall of M. tuberculosis contains the lipid PDIM (phthiocerol dimycocerosates), which is crucial for virulence of the bacterium, but its function is not well understood. Here we show that PDIM expression by M. tuberculosis is negatively regulated by a novel transcriptional repressor, Rv3167c. In addition, we discovered that the escape of M. tuberculosis from its intracellular vacuole was greatly augmented by the presence of PDIM. The increased release of M. tuberculosis into the cytosol led to increased host cell necrosis. The discovery of a link between the cell wall lipid PDIM and a major pathogenesis pathway of M. tuberculosis provides important insights into the molecular mechanisms of host cell manipulation by M. tuberculosis.

scholarly journals Five Genes Encoding Surface-Exposed LPXTG Proteins Are Enriched in Hospital-Adapted Enterococcus faecium Clonal Complex 17 Isolates

2007 ◽  
Vol 189 (22) ◽  
pp. 8321-8332 ◽  
Author(s):  
Antoni P. A. Hendrickx ◽  
Willem J. B. van Wamel ◽  
George Posthuma ◽  
Marc J. M. Bonten ◽  
Rob J. L. Willems
Keyword(s):  
Cell Wall ◽  
Enterococcus Faecium ◽  
Clonal Complex ◽  
Mrna Level ◽  
Surface Protein ◽  
Surface Proteins ◽  
Dot Blot ◽  
Genes Encoding ◽  
Invasive Infections

ABSTRACT Most Enterococcus faecium isolates associated with hospital outbreaks and invasive infections belong to a distinct genetic subpopulation called clonal complex 17 (CC17). It has been postulated that the genetic evolution of CC17 involves the acquisition of various genes involved in antibiotic resistance, metabolic pathways, and virulence. To gain insight into additional genes that may have favored the rapid emergence of this nosocomial pathogen, we aimed to identify surface-exposed LPXTG cell wall-anchored proteins (CWAPs) specifically enriched in CC17 E. faecium. Using PCR and Southern and dot blot hybridizations, 131 E. faecium isolates (40 CC17 and 91 non-CC17) were screened for the presence of 22 putative CWAP genes identified from the E. faecium TX0016 genome. Five genes encoding LPXTG surface proteins were specifically enriched in E. faecium CC17 isolates. These five LPXTG surface protein genes were found in 28 to 40 (70 to 100%) of CC17 and in only 7 to 24 (8 to 26%) of non-CC17 isolates (P < 0.05). Three of these CWAP genes clustered together on the E. faecium TX0016 genome, which may comprise a novel enterococcal pathogenicity island covering E. faecium contig 609. Expression at the mRNA level was demonstrated, and immunotransmission electron microscopy revealed an association of the five LPXTG surface proteins with the cell wall. Minimal spanning tree analysis based on the presence and absence of 22 CWAP genes revealed grouping of all 40 CC17 strains together with 18 hospital-derived but evolutionary unrelated non-CC17 isolates in a distinct CWAP-enriched cluster, suggesting horizontal transfer of CWAP genes and a role of these CWAPs in hospital adaptation.

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