scholarly journals A Review on Microorganisms-Derived Products as Potential Antimicrobial Agents

2021 ◽  
Author(s):  
Alka Rani ◽  
Khem Chand Saini ◽  
Felix Bast ◽  
Sunita Varjani ◽  
Sanjeet Mehariya ◽  
...  
Keyword(s):  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Bioactive Compounds ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
State Of The Art ◽  
Drug Resistant ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Streptomyces Sp

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and micro algae are the auspicious source of vital bioactive compounds. In this review, the existing state of the art re-garding antimicrobial molecules from microorganisms has been summarized. The potential an-timicrobial compounds from actinomycetes, particularly Streptomyces sp.; archaea; fungi including endophytic and marine-derived fungi, mushroom; yeast, and microalgae were briefly described. Furthermore, this review briefly summarized the activity and mode of action of bacteriocins, a ribosomally synthesized antimicrobial peptides product of Eurotium sp., Streptomyces parvulus, S. thermophiles, Lactococcus lactis, etc. Bacteriocins have inherent properties such as targeting multi-ple-drug resistant pathogens, which allows them to be considered next-generation antibiotics. Similarly, Glarea lozoyensis derived antifungal lipohexpeptides i.e., pneumocandins, inhibits 1,3-β-glucan synthase of the fungal cell wall and acts as a precursor for the synthesis of caspo-fungin, is also elaborated. In conclusion, this review highlights the possibility of using microor-ganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical ap-plications. However, more investigations are still required to separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

scholarly journals The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

2021 ◽  
Author(s):  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Gumieniczek ◽  
Maria Malm ◽  
Krzysztof Z. Łączkowski ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Thiazole Derivatives ◽  
Fungal Cell ◽  
Erythrocyte Lysis ◽  
Low Cytotoxicity ◽  
High Antifungal Activity

Abstract Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. Graphical abstract

scholarly journals Length Specificity and Polymerization Mechanism of (1,3)-β-d-Glucan Synthase in Fungal Cell Wall Biosynthesis

Biochemistry ◽  
2020 ◽  
Vol 59 (5) ◽  
pp. 682-693 ◽  
Author(s):  
Abhishek Chhetri ◽  
Anna Loksztejn ◽  
Hai Nguyen ◽  
Kaila M. Pianalto ◽  
Mi Jung Kim ◽  
...  
Keyword(s):  
Cell Wall ◽  
Fungal Cell Wall ◽  
Cell Wall Biosynthesis ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Polymerization Mechanism

scholarly journals Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, againstAspergillusspp.

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Felipe Queiroga Sarmento Guerra ◽  
Rodrigo Santos Aquino de Araújo ◽  
Janiere Pereira de Sousa ◽  
Fillipe de Oliveira Pereira ◽  
Francisco J. B. Mendonça-Junior ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mode Of Action ◽  
Cell Walls ◽  
Coumarin Derivative ◽  
Antifungal Drugs ◽  
Azole Resistance ◽  
Subinhibitory Concentration ◽  
Fungal Cell ◽  
Mycelia Growth

Aspergillusspp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO2), both alone and with antifungal drugs. Its mode of action againstAspergillusspp. Cou-NO2was tested to evaluate its effects on mycelia growth and germination of fungal conidia ofAspergillusspp. We also investigated possible Cou-NO2action on cell walls (0.8 M sorbitol) and on Cou-NO2to ergosterol binding in the cell membrane. The study shows that Cou-NO2is capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NO2enhanced thein vitroeffects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole) Cou-NO2displays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent againstAspergillusspecies.

scholarly journals The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in Aspergillus fumigatus

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Yuan Chen ◽  
Francois Le Mauff ◽  
Yan Wang ◽  
Ruiyang Lu ◽  
Donald C. Sheppard ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Aspergillus Fumigatus ◽  
Biofilm Formation ◽  
Wall Stress ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Content Type ◽  
Cell Wall Stress ◽  
Chitin Synthases

ABSTRACT Polysaccharides are key components of both the fungal cell wall and biofilm matrix. Despite having distinct assembly and regulation pathways, matrix exopolysaccharide and cell wall polysaccharides share common substrates and intermediates in their biosynthetic pathways. It is not clear, however, if the biosynthetic pathways governing the production of these polysaccharides are cooperatively regulated. Here, we demonstrate that cell wall stress promotes production of the exopolysaccharide galactosaminogalactan (GAG)-depend biofilm formation in the major fungal pathogen of humans Aspergillus fumigatus and that the transcription factor SomA plays a crucial role in mediating this process. A core set of SomA target genes were identified by transcriptome sequencing and chromatin immunoprecipitation coupled to sequencing (ChIP-Seq). We identified a novel SomA-binding site in the promoter regions of GAG biosynthetic genes agd3 and ega3, as well as its regulators medA and stuA. Strikingly, this SomA-binding site was also found in the upstream regions of genes encoding the cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Thus, SomA plays a direct regulation of both GAG and cell wall polysaccharide biosynthesis. Consistent with these findings, SomA is required for the maintenance of normal cell wall architecture and compositions in addition to its function in biofilm development. Moreover, SomA was found to globally regulate glucose uptake and utilization, as well as amino sugar and nucleotide sugar metabolism, which provides precursors for polysaccharide synthesis. Collectively, our work provides insight into fungal adaptive mechanisms in response to cell wall stress where biofilm formation and cell wall homeostasis were synchronously regulated. IMPORTANCE The cell wall is essential for fungal viability and is absent from human hosts; thus, drugs disrupting cell wall biosynthesis have gained more attention. Caspofungin is a member of a new class of clinically approved echinocandin drugs to treat invasive aspergillosis by blocking β-1,3-glucan synthase, thus damaging the fungal cell wall. Here, we demonstrate that caspofungin and other cell wall stressors can induce galactosaminogalactan (GAG)-dependent biofilm formation in the human pathogen Aspergillus fumigatus. We further identified SomA as a master transcription factor playing a dual role in both biofilm formation and cell wall homeostasis. SomA plays this dual role by direct binding to a conserved motif upstream of GAG biosynthetic genes and genes involved in cell wall stress sensors, chitin synthases, and β-1,3-glucan synthase. Collectively, these findings reveal a transcriptional control pathway that integrates biofilm formation and cell wall homeostasis and suggest SomA as an attractive target for antifungal drug development.

scholarly journals Measuring thousands of single vesicle leakage events reveals the mode of action of antimicrobial peptides

2021 ◽  
Author(s):  
Kareem Al Nahas ◽  
Marcus Fletcher ◽  
Katharine Hammond ◽  
Christian Nehls ◽  
Jehangir Cama ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Host Defense ◽  
Mode Of Action ◽  
Antimicrobial Agents ◽  
Spatiotemporal Resolution ◽  
Detailed Understanding ◽  
Modes Of Action ◽  
Structure Activity ◽  
Single Vesicle

Host defense or antimicrobial peptides hold promise for providing new pipelines of effective antimicrobial agents. Their activity quantified against model phospholipid membranes is fundamental to a detailed understanding of their structure-activity relationships. However, existing characterization assays lack the resolution necessary to achieve this insight. Leveraging a highly parallelized microfluidic platform for trapping and studying thousands of giant unilamellar vesicles, we conducted quantitative long-term microscopy studies to monitor the membrane-disruptive activity of archetypal antimicrobial peptides with a high spatiotemporal resolution. We described the modes of action of these peptides via measurements of the disruption of the vesicle population under the conditions of continuous peptide dosing using a range of concentrations, and related the observed modes with the molecular activity mechanisms of these peptides. The study offers an effective approach for characterizing membrane-targeting antimicrobial agents in a standardized manner, and for assigning specific modes of action to the corresponding antimicrobial mechanisms.

scholarly journals Transcriptional Profiling Reveals that Daptomycin Induces the Staphylococcus aureus Cell Wall Stress Stimulon and Genes Responsive to Membrane Depolarization

2007 ◽  
Vol 52 (3) ◽  
pp. 980-990 ◽  
Author(s):  
Arunachalam Muthaiyan ◽  
Jared A. Silverman ◽  
Radheshyam K. Jayaswal ◽  
Brian J. Wilkinson
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Mode Of Action ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Transcriptional Profiling ◽  
Wall Stress ◽  
Membrane Depolarization ◽  
Transcriptional Responses ◽  
Cell Wall Stress

ABSTRACT Daptomycin is a lipopeptide antibiotic that has recently been approved for treatment of gram-positive bacterial infections. The mode of action of daptomycin is not yet entirely clear. To further understand the mechanism transcriptomic analysis of changes in gene expression in daptomycin-treated Staphylococcus aureus was carried out. The expression profile indicated that cell wall stress stimulon member genes (B. J. Wilkinson, A. Muthaiyan, and R. K. Jayaswal, Curr. Med. Chem. Anti-Infect. Agents 4:259-276, 2005) were significantly induced by daptomycin and by the cell wall-active antibiotics vancomycin and oxacillin. Comparison of the daptomycin response of a two-component cell wall stress stimulon regulator VraSR mutant, S. aureus KVR, to its parent N315 showed diminished expression of the cell wall stress stimulon in the mutant. Daptomycin has been proposed to cause membrane depolarization, and the transcriptional responses to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nisin were determined. Transcriptional profiles of the responses to these antimicrobial agents showed significantly different patterns compared to those of the cell wall-active antibiotics, including little or no induction of the cell wall stress stimulon. However, there were a significant number of genes induced by both CCCP and daptomycin that were not induced by oxacillin or vancomycin, so the daptomycin transcriptome probably reflected a membrane depolarizing activity of this antimicrobial also. The results indicate that inhibition of peptidoglycan biosynthesis, either directly or indirectly, and membrane depolarization are parts of the mode of action of daptomycin.

scholarly journals Drug Interaction Studies of a Glucan Synthase Inhibitor (LY 303366) and a Chitin Synthase Inhibitor (Nikkomycin Z) for Inhibition and Killing of Fungal Pathogens

2000 ◽  
Vol 44 (9) ◽  
pp. 2547-2548 ◽  
Author(s):  
David A. Stevens
Keyword(s):  
Cell Wall ◽  
Fungal Pathogens ◽  
Enzyme Inhibitors ◽  
Chitin Synthase ◽  
Synergistic Activity ◽  
Fungal Cell ◽  
Glucan Synthase ◽  
Nikkomycin Z ◽  
Synthase Inhibitor

ABSTRACT The interaction between inhibitors of components of the fungal cell wall, glucan and chitin, was studied in vitro with the respective synthase enzyme inhibitors LY 303366 and nikkomycin Z. WithAspergillus fumigatus synergy was noted for inhibition and killing, and synergistic activity was also noted for some isolates of other species presently regarded as difficult to treat.

scholarly journals FLO11Gene Is Involved in the Interaction of Flor Strains of Saccharomyces cerevisiae with a Biofilm-Promoting Synthetic Hexapeptide

2013 ◽  
Vol 79 (19) ◽  
pp. 6023-6032 ◽  
Author(s):  
Marc Bou Zeidan ◽  
Lourdes Carmona ◽  
Severino Zara ◽  
Jose F. Marcos
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Antimicrobial Peptides ◽  
Gene Knockout ◽  
Yeast Cells ◽  
Knockout Mutant ◽  
Fungal Cell ◽  
Content Type ◽  
Cell Penetrating ◽  
Flor Yeasts

ABSTRACTSaccharomyces cerevisiae“flor” yeasts have the ability to form a buoyant biofilm at the air-liquid interface of wine. The formation of biofilm, also called velum, depends onFLO11gene length and expression.FLO11encodes a cell wall mucin-like glycoprotein with a highly O-glycosylated central domain and an N-terminal domain that mediates homotypic adhesion between cells. In the present study, we tested previously known antimicrobial peptides with different mechanisms of antimicrobial action for their effect on the viability and ability to form biofilm ofS. cerevisiaeflor strains. We found that PAF26, a synthetic tryptophan-rich cationic hexapeptide that belongs to the class of antimicrobial peptides with cell-penetrating properties, but not other antimicrobial peptides, enhanced biofilm formation without affecting cell viability in ethanol-rich medium. The PAF26 biofilm enhancement required a functionalFLO11but was not accompanied by increasedFLO11expression. Moreover, fluorescence microscopy and flow cytometry analyses showed that the PAF26 peptide binds flor yeast cells and that aflo11gene knockout mutant lost the ability to bind PAF26 but not P113, a different cell-penetrating antifungal peptide, demonstrating that theFLO11gene is selectively involved in the interaction of PAF26 with cells. Taken together, our data suggest that the cationic and hydrophobic PAF26 hexapeptide interacts with the hydrophobic and negatively charged cell wall, favoring Flo11p-mediated cell-to-cell adhesion and thus increasing biofilm biomass formation. The results are consistent with previous data that point to glycosylated mucin-like proteins at the fungal cell wall as potential interacting partners for antifungal peptides.

scholarly journals FsFKS1, the 1,3-β-Glucan Synthase from the Caspofungin-Resistant Fungus Fusarium solani

2006 ◽  
Vol 5 (7) ◽  
pp. 1036-1042 ◽  
Author(s):  
Young-sil Ha ◽  
Sarah F. Covert ◽  
Michelle Momany
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Fusarium Solani ◽  
Cell Walls ◽  
Clinical Isolates ◽  
Fungal Cell ◽  
Spore Viability ◽  
Glucan Synthase ◽  
Main Components ◽  
Sensitive Fungus

ABSTRACT The cell wall, a mesh of carbohydrates and proteins, shapes and protects the fungal cell. The enzyme responsible for the synthesis of one of the main components of the fungal wall, 1,3-β-glucan synthase, is targeted by the antifungal caspofungin acetate (CFA). Clinical isolates of Candida albicans and Aspergillus fumigatus are much more sensitive to CFA than clinical isolates of Fusarium species. To better understand CFA resistance in Fusarium species, we cloned and sequenced FsFKS1, which encodes the Fusarium solani f. sp. pisi β(1,3)-d-glucan synthase, used RNA interference to reduce its expression and complemented deletion of the essential fks gene of the CFA-sensitive fungus A. fumigatus with FsFKS1. Reduction of the FsFKS1 message in F. solani f. sp. pisi reduced spore viability and caused lysis of spores and hyphae, consistent with cell wall defects. Compensating for the loss of A. fumigatus fks1 with FsFKS1 caused only a modest increase in the tolerance of A. fumigatus for CFA. Our results suggest that FsFKS1 is required for the proper construction of F. solani cell walls and that the resistance of F. solani to CFA is at best only partially due to resistance of the FsFKS1 enzyme to this antifungal agent.

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