Fungal cell wall: An underexploited target for antifungal therapies

Ibe, Chibuike; Munro, Carol A.

doi:10.1371/journal.ppat.1009470

Cited by 57 publications

(30 citation statements)

References 32 publications

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“…Candida albicans cells experience elevated chitin content in their wall as a consequence of an adaptive (remodeling) mechanism to maintain intact (i.e., not permeable) the cell walls and to fix resistance to specific drugs that inhibit synthesis of β-1, 3-glucans (i.e., echinocandins) ( Ibe and Munro, 2021 ). The same chitin-enrichment remodeling effect was also found in C. auris species; however, the extent of such effect was significantly less pronounced ( Lara-Aguilar et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…Building upon this automatic indicator, we compared the relative intensities of chitin-related bands (with respect to the 478 cm −1 glucose ring band) among different Candida clades and found that C. albicans was richer in chitin by ∼31 and 50% as compared to Clades III and II C. auris, respectively. Since chitin adds rigidity Candida albicans cells experience elevated chitin content in their wall as a consequence of an adaptive (remodeling) mechanism to maintain intact (i.e., not permeable) the cell walls and to fix resistance to specific drugs that inhibit synthesis of β-1, 3-glucans (i.e., echinocandins) (Ibe and Munro, 2021). The same chitin-enrichment remodeling effect was also found in C. auris species; however, the extent of such effect was significantly less pronounced (Lara-Aguilar et al, 2021).…”

Section: Average Raman Spectra From Different Candida Speciesmentioning

confidence: 99%

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Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification

et al. 2021

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Invasive fungal infections caused by yeasts of the genus Candida carry high morbidity and cause systemic infections with high mortality rate in both immunocompetent and immunosuppressed patients. Resistance rates against antifungal drugs vary among Candida species, the most concerning specie being Candida auris, which exhibits resistance to all major classes of available antifungal drugs. The presently available identification methods for Candida species face a severe trade-off between testing speed and accuracy. Here, we propose and validate a machine-learning approach adapted to Raman spectroscopy as a rapid, precise, and labor-efficient method of clinical microbiology for C. auris identification and drug efficacy assessments. This paper demonstrates that the combination of Raman spectroscopy and machine learning analyses can provide an insightful and flexible mycology diagnostic tool, easily applicable on-site in the clinical environment.

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Section: Resultsmentioning

confidence: 99%

Section: Average Raman Spectra From Different Candida Speciesmentioning

confidence: 99%

Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification

et al. 2021

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“…One of the main components of the cell wall mannoproteins are glycosylphosphatidylinositol (GPI)-modified proteins, including proteins with glycosylhydrolase, glycosyltransferase, or transglycosidase activities. Those enzymes are included in cell wall synthesis, thus are attractive antifungal targets since inhibiting their synthesis and localization to the cell wall could stroke on virulence and cell wall biosynthesis significantly [ 136 ].…”

Section: Recent Update On Antifungal Targets and Strategiesmentioning

confidence: 99%

“…They are productive at low concentrations against Fusarium , Aspergillus , Candida , and Scedosporium species. APX001A is effective against caspofungin-resistant C. albicans and C. auris [ 136 , 140 ]. Magnoflorine (50 μg/mL) inhibited more than 50% of the activity of alpha-glucosidase, an enzyme essential for normal cell wall composition and C. albicans virulence, also displaying antibiofilm potential [ 78 ].…”

Section: Recent Update On Antifungal Targets and Strategiesmentioning

confidence: 99%

Emerging Antifungal Targets and Strategies

Ivanov

Ćirić

Stojković

2022

IJMS

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Despite abundant research in the field of antifungal drug discovery, fungal infections remain a significant healthcare burden. There is an emerging need for the development of novel antifungals since those currently available are limited and do not completely provide safe and secure protection. Since the current knowledge regarding the physiology of fungal cells and the infection mechanisms is greater than ever, we have the opportunity to use this for the development of novel generations of antifungals. In this review, we selected and summarized recent studies describing agents employing different antifungal mechanisms. These mechanisms include interference with fungal resistance, including impact on the efflux pumps and heat shock protein 90. Additionally, interference with virulence factors, such as biofilms and hyphae; the impact on fungal enzymes, metabolism, mitochondria, and cell wall; and antifungal vaccines are explored. The agents investigated belong to different classes of natural or synthetic molecules with significant attention given also to plant extracts. The efficacy of these antifungals has been studied mainly in vitro with some in vivo, and clinical studies are needed. Nevertheless, there is a large quantity of products employing novel antifungal mechanisms that can be further explored for the development of new generation of antifungals.

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“…There are antifungal agents that inhibit the fungal cell wall by targeting glucan, chitin, and mannan proteins [4][5][6][7][8]. In consequence of the fungal cell wall becoming resistant to antifungal agents, the causes of this resistance have been investigated and new treatments have been developed [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

S. cerevisiae Outer and Inner Membranes are Compromised upon Benzyl Alcohol Treatment

Ergüden¹

2021

Int. J. Membrane Sci. Techno.

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Although there are innovations in the treatment of diseases caused by fungi and medicines with multiple targets have been developed, the search for a drug with a broad spectrum and without any side effects continues to date. It is generally accepted that determining the cellular target responsible for the toxic effect opens up new possibilities for the development of new drugs. Especially the effects of antifungal agents on the surface components of the fungal cell, on cell wall synthesis and the identification of the target site are crucial in antifungal drug development. Thus studies on the fungal cell membranes in connection with the antifungal agents, aim to develop new strategies for the therapy of fungal infections. Antifungal agents targeting fungal cell wall and cell membrane components have increased in importance in clinical studies. In this study, understanding the mechanism of action of benzyl alcohol, a known membrane fluidizer, and the determination of its cellular targets are aimed. We have shown that in the presence of sorbitol, the osmotic stabilizer, benzyl alcohol becomes less effective against yeast cell. Moreover, benzyl alcohol disrupts cell membrane, causing leakage of ions to the extracellular medium. Nuclear membrane is distorted upon treatment of yeast cells with benzyl alcohol. Thus, we conclude that both outer and inner yeast cell membranes are compromised by the action of benzyl alcohol.

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Fungal cell wall: An underexploited target for antifungal therapies

Cited by 57 publications

References 32 publications

Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification

Raman Imaging of Pathogenic Candida auris: Visualization of Structural Characteristics and Machine-Learning Identification

Emerging Antifungal Targets and Strategies

S. cerevisiae Outer and Inner Membranes are Compromised upon Benzyl Alcohol Treatment

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