Spices as Eco-friendly Microbicides: From Kitchen to Clinic
Mahendra Rai, Chistiane M. Feitosa in Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
The fungal cell wall is a dynamic structure that protects fungal protoplasts from external osmotic shocks and defines fungal morphogenesis. Thus, changes in the organization or functional disruption of the cell wall induced by antifungal agents are involved in fungal death. The fungal cell membrane is a dynamic structure composed of a lipid bilayer where enzymes and transport proteins are embedded. Ergosterol is a unique sterol found only in the cell membrane of fungi, important for their proper growth and functioning and also acts as an important regulator of membrane fluidity. Thymol have been shown to decrease ergosterol in cell membranes of Candida and Cryptococcus, thereby causing disruption of membrane integrity, membrane-associated enzyme disturbances, extensive damage and, finally cell death (Kowalczyk et al. 2020). Similarly eugenol exerts its antifungal activity on the cell wall and cell membrane of Trichophyton rubrum by disrupting ergosterol biosynthesis and such a result may serve as a guide for future in vivo studies of clinical use of eugenol in treating dermatophyte infections (de Oliveira Pereira et al. 2013).
Fungi and Water
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
Fungi have cell walls similar to plants and are different from animals. The fungal cell wall is composed of chitin that gives shape, form, and rigidity to fungi. It protects against mechanical injury, prevents osmotic lysis, and provides passive protection against the ingress of potentially harmful macromolecules (2–3). Chitin is a polymer of N-acetyl-D-glucosamine. The major polysaccharides of the cell wall matrix consist of non-cellulosic glucans such as glycogen-like compounds, mannans (polymers of mannose), chitosan (polymers of glucosamine), and galactans (polymers of galactose). Small amounts of fucose, rhamnose, xylose, and uronic acids may be present (2). Glucan refers to a large group of D-glucose polymers having glycosidic bonds. Insoluble β-glucans are apparently amorphous in the cell wall. Yeast cell wall is composed of three layers and is about 200- to 600-nm thick. Its inner surface is chitinous, and its outer layer contains α-glucan (2). In addition to chitin, glucan, and mannan, cell walls may contain lipid, protein, chitosan, acid phosphatase, α-amylase, protease, melanin, and inorganic ions such as phosphorus, calcium, and magnesium (2). The fungal wall also protects cells against mechanical injury and blocks the ingress of toxic macromolecules. The fungal cell wall is also essential to prevent osmotic lysis. Even a small lesion in the cell wall can result in extrusion of cytoplasm due to the internal (turgor) pressure of the protoplast. The cell membrane of a fungus has a unique sterol and ergosterol (3).
Caspofungin
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Pathways regulating the synthesis and repair of the fungal cell wall are fairly complex and highly redundant, which is not surprising given the dynamic and important role of the cell wall for maintaining cellular physiology (Lesage and Bussey, 2006). Echinocandin depletion of glucan fibrils in the cell wall of susceptible fungi activates a key regulatory protein, Rho1, and the PKC signaling pathway, which in turn upregulate multiple cell wall biosynthesis and stress-response pathways that counteract the effects of glucan synthase inhibition (Lesage and Bussey, 2006; Reinoso-Martín et al., 2003). Echinocandin-mediated damage to the cell wall induces the membrane-spanning sensor Wsc1 and activates Slt2 signaling, which initiates a protective response through de novo cell wall synthesis and increased dumping of chitin in the cell wall (Figure 146.3) (Ene et al., 2015; Lee et al., 2012; Walker et al., 2013; Walker et al., 2015).
Exogenous fungal quorum sensing molecules inhibit planktonic cell growth and modulate filamentation and biofilm formation in the Sporothrix schenckii complex
Published in Biofouling, 2020
Raimunda Sâmia Nogueira Brilhante, Vandbergue Santos Pereira, Augusto Feynman Dias Nobre, Jonathas Sales de Oliveira, Mirele Rodrigues Fernandes, Anderson da Cunha Costa, Anderson Messias Rodrigues, Zoilo Pires de Camargo, Waldemiro Aquino Pereira-Neto, José Júlio Costa Sidrim, Marcos Fábio Gadelha Rocha
In general, the MICs of farnesol, 2-phenylethanol and tyrosol against the yeast form of Sporothrix spp. were 2- or 4-fold lower than those obtained for the filamentous form. This difference in susceptibility is common and has been observed in several studies that evaluated both morphological presentations of this fungus (Gutierrez-Galhardo et al. 2010; Sanchotene et al. 2017; Brilhante et al. 2018b). The divergence in susceptibility may be related to the difference in fungal cell wall constituent proportions between the filamentous and yeast forms of Sporothrix spp., in particular glucosamine, glucose and β-1,3-glucan (Martínez-Álvarez et al. 2017). The cell wall is an important structure for the growth of fungi since it confers osmotic stability and protects against stress. In addition, this structure is responsible for maintaining the cell shape. Changes in cell wall structure have been related to decreased AMB susceptibility in Candida spp. (Mesa-Arango et al. 2016). Thus, it can be hypothesized that differences in the cell wall composition between filamentous and yeast forms of Sporothrix spp. may influence the susceptibility to drugs.
Echinocandins – structure, mechanism of action and use in antifungal therapy
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mateusz Szymański, Sandra Chmielewska, Urszula Czyżewska, Marta Malinowska, Adam Tylicki
Echinocandins have become a good alternative to azoles and polyenes in the treatment of severe fungal infections caused in particular by Candida and Aspergillus species due to their unique mechanism of action and relatively mild side effects compared to other antifungal drugs. These antibiotics block the synthesis of one of the main components of the fungal cell wall (β-(1,3)-d-glucan) by binding to the Fks subunit of β-(1,3)-d-glucan synthase. Their action results in cell wall defects and the death of fungal cells. The metabolic pathway that echinocandins targets does not occur in human cells, which limits side effects. They are also administered to patients with a weakened immune system, e.g. people suffering from AIDS, cancer, neutropenia, as well as to transplant patients who are particularly at risk of fungal infections due to immunosuppressive therapy. On the other hand, echinocandins are administered only intravenously, which limits the treatment process only to hospital conditions. They are also embryotoxic so they cannot be administered to pregnant women. They are also not effective in the treatment of fungal infections caused by species with limited content of β-(1,3)-d-glucan in the cell wall.
Subtle relationships between Pseudomonas aeruginosa and fungi in patients with cystic fibrosis
Published in Acta Clinica Belgica, 2022
Kaicheng Yan, Hong Yin, Jin Wang, Yun Cai
In PA and other Pseudomonas species, Rhls are usually produced in the form of a mixture of homologous di- and mono-Rhls in terms of the length of the lipid chain [46]. During nutritional restriction (e.g. iron starvation), PA can over-generate Rhls in vitro [47]. The inhibition of AF growth and the increase of AF cell wall thickness are attributed to the secretion of diRhls, which inhibit fungal β-1,3-glucanase (GS) [48]. When growing in the presence of PA, AF shows a thick cell wall. The results suggest that bacterial co-culture induces the modification of fungal cell wall structure. In the presence of diRhls, the decreased growth of AF and its morphology change are attributed to the inhibition of β-1,3-GS by diRhls. The specific inhibition of diRhls against fungal GS activity results in the modified nature of fungal extracellular matrix surrounding the AF hyphae, inhibits the growth of AF and induces the formation of short multibranched hyphae.