Had1 Is Required for Cell Wall Integrity and Fungal Virulence inCryptococcus neoformans

AbstractPlant fungal pathogens secrete numerous proteins into the apoplast at the plant–fungus contact sites to facilitate colonization. Only a few secreted proteins were functionally characterized in Magnaporthe oryzae, the fungal pathogen causing rice blast disease worldwide. ALG3 is an α-1, 3-mannosyltransferase function in N-glycan synthesis for secreted N-glycosylated proteins, and the Δalg3 mutants show strong defects in cell wall integrity and fungal virulence, indicating a potential effect on the secretion of multiple proteins. In this study, we compared the secretome of wild type and Δalg3 mutants, and identified 51 proteins that require ALG3 for proper secretion. These are predicted to be involved in metabolic processes, interspecies interactions, cell wall organization, and response to chemicals. The tested secreted proteins localized at the apoplast region surrounding the fungal infection hyphae. Moreover, the N-glycosylation of candidate proteins was significantly changed in the Δalg3 mutant, leading to the reduction of protein secretion and abnormal protein localization. Furthermore, we tested the function of two genes, one is a previously reported M. oryzae gene Invertase 1 (INV1) encoding a secreted invertase, and the other one is a gene encoding an Acid mammalian chinitase (AMCase). The fungal virulence was significantly reduced and the cell wall integrity was altered in the Δinv1 and Δamcase mutant strains. Elucidation of the comparative secretome of M. oryzae improves our understanding of the proteins that require ALG3 for secretion, and of their function in fungal virulence and cell wall integrity.

Download Full-text

Faculty Opinions recommendation of Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.6491958.6618056 ◽

2010 ◽

Author(s):

Paula Sundstrom

Keyword(s):

Cell Wall ◽

Aspergillus Fumigatus ◽

Fungal Pathogen ◽

Cell Wall Integrity ◽

Fungal Virulence ◽

Human Fungal Pathogen ◽

Trehalose Biosynthesis

Download Full-text

Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus

Molecular Microbiology ◽

10.1111/j.1365-2958.2010.07254.x ◽

2010 ◽

pp. no-no ◽

Cited By ~ 25

Author(s):

Srisombat Puttikamonkul ◽

Sven D. Willger ◽

Nora Grahl ◽

John R. Perfect ◽

Navid Movahed ◽

...

Keyword(s):

Cell Wall ◽

Aspergillus Fumigatus ◽

Fungal Pathogen ◽

Cell Wall Integrity ◽

Fungal Virulence ◽

Human Fungal Pathogen ◽

Trehalose Biosynthesis

Download Full-text

Faculty Opinions recommendation of The metabolic enzyme ManA reveals a link between cell wall integrity and chromosome morphology.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7618956.7924054 ◽

2011 ◽

Author(s):

Susan Golden ◽

Susan Cohen

Keyword(s):

Cell Wall ◽

Chromosome Morphology ◽

Cell Wall Integrity ◽

Metabolic Enzyme

Download Full-text

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

Current Proteomics ◽

10.2174/1570164615666180820155807 ◽

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.

Download Full-text

Soybean germination limits the role of cell wall integrity in controlling protein physicochemical changes during cooking and improves protein digestibility

Food Research International ◽

10.1016/j.foodres.2021.110254 ◽

2021 ◽

Vol 143 ◽

pp. 110254

Author(s):

Mostafa Zahir ◽

Vincenzo Fogliano ◽

Edoardo Capuano

Keyword(s):

Cell Wall ◽

Protein Digestibility ◽

Cell Wall Integrity ◽

Physicochemical Changes

Download Full-text

The N-mannosyltransferase gene BbAlg9 contributes to cell wall integrity, fungal development and the pathogenicity of Beauveria bassiana

Fungal Biology ◽

10.1016/j.funbio.2021.04.011 ◽

2021 ◽

Author(s):

Ji-Zheng Song ◽

Ya-Ping Yin ◽

Wen Cheng ◽

Jia-Hua Liu ◽

Shun-Juan Hu ◽

...

Keyword(s):

Cell Wall ◽

Beauveria Bassiana ◽

Cell Wall Integrity ◽

Fungal Development

Download Full-text

Yeast Nap1-Binding Protein Nbp2p Is Required for Mitotic Growth at High Temperatures and for Cell Wall Integrity

Genetics ◽

10.1093/genetics/165.2.517 ◽

2003 ◽

Vol 165 (2) ◽

pp. 517-529

Author(s):

Kentaro Ohkuni ◽

Asuko Okuda ◽

Akihiko Kikuchi

Keyword(s):

Cell Death ◽

Cell Wall ◽

High Temperature ◽

High Temperatures ◽

Hybrid System ◽

Mapk Pathway ◽

Binding Protein ◽

Cell Wall Integrity ◽

Calcofluor White ◽

Two Hybrid

AbstractNbp2p is a Nap1-binding protein in Saccharomyces cerevisiae identified by its interaction with Nap1 by a two-hybrid system. NBP2 encodes a novel protein consisting of 236 amino acids with a Src homology 3 (SH3) domain. We showed that NBP2 functions to promote mitotic cell growth at high temperatures and cell wall integrity. Loss of Nbp2 results in cell death at high temperatures and in sensitivity to calcofluor white. Cell death at high temperature is thought not to be due to a weakened cell wall. Additionally, we have isolated several type-2C serine threonine protein phosphatases (PTCs) as multicopy suppressors and MAP kinase-kinase (MAPKK), related to the yeast PKC MAPK pathway, as deletion suppressors of the nbp2Δ mutant. Screening for deletion suppressors is a new genetic approach to identify and characterize additional proteins in the Nbp2-dependent pathway. Genetic analyses suggested that Ptc1, which interacts with Nbp2 by the two-hybrid system, acts downstream of Nbp2 and that cells lacking the function of Nbp2 prefer to lose Mkk1, but the PKC MAPK pathway itself is indispensable when Nbp2 is deleted at high temperature.

Download Full-text

Putative PmrA and PmcA are important for normal growth, morphogenesis and cell wall integrity, but not for viability in Aspergillus nidulans

Microbiology ◽

10.1099/mic.0.080119-0 ◽

2014 ◽

Vol 160 (11) ◽

pp. 2387-2395 ◽

Cited By ~ 7

Author(s):

Hechun Jiang ◽

Feifei Liu ◽

Shizhu Zhang ◽

Ling Lu

Keyword(s):

Cell Wall ◽

Plasma Membrane ◽

Aspergillus Nidulans ◽

Normal Growth ◽

Cell Wall Integrity ◽

Plasma Membrane Atpase ◽

Growth Defects ◽

Double Deletion ◽

Intracellular Ca ◽

P Type

P-type Ca2+-transporting ATPases are Ca2+ pumps, extruding cytosolic Ca2+ to the extracellular environment or the intracellular Ca2+ store lumens. In budding yeast, Pmr1 (plasma membrane ATPase related), and Pmc1 (plasma membrane calcium-ATPase) cannot be deleted simultaneously for it to survive in standard medium. Here, we deleted two putative Ca2+ pumps, designated AnPmrA and AnPmcA, from Aspergillus nidulans, and obtained the mutants ΔanpmrA and ΔanpmcA, respectively. Then, using ΔanpmrA as the starting strain, the promoter of its anpmcA was replaced with the alcA promoter to secure the mutant ΔanpmrAalcApmcA or its anpmcA was deleted completely to produce the mutant ΔanpmrAΔpmcA. Different from the case in Saccharomyces cerevisiae, double deletion of anpmrA and anpmcA was not lethal in A. nidulans. In addition, deletion of anpmrA and/or anpmcA had produced growth defects, although overexpression of AnPmc1 in ΔanpmrAalcApmcA could not restore the growth defects that resulted from the loss of AnPmrA. Moreover, we found AnPmrA was indispensable for maintenance of normal morphogenesis, especially in low-Ca2+/Mn2+ environments. Thus, our findings suggest AnPmrA and AnPmcA might play important roles in growth, morphogenesis and cell wall integrity in A. nidulans in a different way from that in yeasts.

Download Full-text