China
Africa
Explore chapters and articles related to this topic
Malassezia
Published in Rossana de Aguiar Cordeiro, Pocket Guide to Mycological Diagnosis, 2019
Reginaldo Gonçalves de Lima-Neto, Danielle Patrícia Cerqueira Macêdo, Ana Maria Rabelo de Carvalho, Carolina Maria da Silva, Rejane Pereira Neves
As previously mentioned, proper identification of Malassezia species can be attained by molecular methods. Many molecular tools have been established for Malassezia identification and also for the detection of intraspecific genetic variation: (a) direct sequencing of rDNA loci (internal transcribed spacers ITS-1 and ITS-2, intergenic spacer IGS-1, large subunit LSU), chitin synthase gene and RNA polymerase subunit 1 gene, (b) PCR-based restriction fragment length polymorphism (PCR-RFLP) of rDNA loci, (c) random amplification of polymorphic DNA (RAPD), (d) denaturing gradient gel electrophoresis (DGGE), and (e) pulsed field gel electrophoresis (PFGE) (Cafarchia et al., 2011). Molecular methods suitable for identification of Malassezia species in clinical mycological laboratories are described in Table 6.3.
Antifungal drug resistance: Significance and mechanisms
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Sharvari Dharmaiah, Rania A. Sherif, Pranab K. Mukherjee
Some studies have suggested that modulation of echinocandin susceptibility is associated with differential expression of overlapping set of genes involved in FKS regulation, compensatory chitin synthesis, protein mannosylation, and the protein kinase C1 (Pkc1)-dependent cell integrity pathway [213,214]. Osherov et al. [215] proposed over-expression of SBE2 (which encodes Sbe2p, a Golgi protein involved in the transport of cell wall components) as an adaptive mechanism of resistance against echinocandins. These investigators showed that over-expression of Sbe2p resulted in caspofungin resistance in S. cerevisiae, and that deletion of SBE2 rendered the yeast hypersensitive to caspofungin, thus showing that over-expression of Sbe2p imparts caspofungin resistance. Walker et al. [216] reported that treatment of C. albicans with low levels of echinocandins stimulated expression of the gene encoding chitin synthase (CHS), increased activity of this enzyme, elevated chitin content and rendered the cells less susceptible. The role of substrate availability in echinocandin resistance is also underscored by the study performed by Feldmesser et al. [217], who showed that inactivity of caspofungin against C. neoformans is largely due to difference in glucan structure in this fungus, which contains both 1,3 β-d-glucan and 1,6 β-d-glucan in the cell wall.
Lipids of Aspergillus
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
P. Chakrabarti, M. Kundu, J. Basu
The organophosphorus fungicides, iprobenfos and edifenphos, inhibit the germination of spores of A. nidulans13. In A. nidulans, iprobenfos caused a 70% increase in PE concentration and a 90% inhibition of chitin synthetase activity, accompanied by abnormal hyphae formation. Fungizone treatment74 also leads to a decrease in total lipids, free sterols, sterol esters and triacylglycerols.
Existing and emerging therapies for the treatment of invasive candidiasis and candidemia
Published in Expert Opinion on Emerging Drugs, 2022
David De Bels, Evelyne Maillart, Françoise Van Bambeke, Sebastien Redant, Patrick M. Honoré
The last class of antifungals acting on a new target in Candida are polyoxins, with nikkomycin being the only drug under clinical development since more than 15 years, asking question about its potential future. It is a competitive inhibitor of chitin synthase, an essential structural component of fungal cell walls [95]. It shows fungicidal activity against endemic dimorphic fungi, including Coccidiosis’s, Histoplasma, and Blastomyces spp, but inconstant activity against other fungi, with MIC ranging from 0.125 to >64 mg/L. MIC50 and MIC90 are respectively 2 and 32 mg/L for C. auris [96]. Nikkomycin it thus mainly used in combination with amphotericin B, azoles, or echinocandins, allowing to observe synergistic effects against a range of medically important fungi [97,98]. The first three phase 1 trials have been only recently completed. Drug dosage were tested between 50 mg BID to 750 mg TID or ones orally between 250 mg to 2,000 mg [99].
The antifungal activity of caspofungin in combination with antifungals or non-antifungals against Candida species in vitro and in clinical therapy
Published in Expert Review of Anti-infective Therapy, 2022
Shan Su, Haiying Yan, Li Min, Hongmei Wang, Xueqi Chen, Jinyi Shi, Shujuan Sun
Nikkomycin Z, which is undergoing a clinical trial for treating fungal infections, is a specific chitin synthase inhibitor. A recent study demonstrated the combined antifungal effects of Nikkomycin Z and caspofungin against Saccharomyces cerevisiae (S. cerevisiae) (WT BY4741). The MIC of Nikkomycin Z was reduced from 12.5 µg/mL to 3.125 µg/mL, the MIC of caspofungin was reduced from 0.03 µg/mL to 0.00625 µg/mL, and the FICI was 0.4583 [50]. Another study demonstrated that the combination of caspofungin and nikkomycin Z caused extended cell death and that the structure of the biofilm was sparse compared to the control. This drug combination showed synergistic effects against three of five total caspofungin-susceptible C. albicans isolates (n = 5, there were five isolates in total) and one caspofungin-resistant C. albicans isolate [51]. Two new potential antifungal compounds, IMB-D10 and IMB-F4, were isolated based on a chemical genetic method. They inhibited the activity of chitin synthase in vitro and reduced chitin levels in yeast cells. The antifungal effects of caspofungin were detected, and IMB-F4 exhibited excellent activity with FICI < 0.5 [50].
Triflumuron induces genotoxicity in both mice bone marrow cells and human Colon cancer cell line
Published in Toxicology Mechanisms and Methods, 2020
Rim Timoumi, Ines Amara, Yossra Ayed, Intidhar Ben Salem, Salwa Abid-Essefi
TFM acts by inhibiting chitin synthesis. It prevents the insertion of N-acetylglucosamine into the biosynthesis of chitin. Indeed, chitin is a linear polymer composed of N-acetyl-glucosamines. The biosynthesis of this polymer involves several enzymes to convert different sugars (glucose, trehalose) into UPD-N-acetyl-glucosamine (Merzendorfer 2011). The last step is synthesized by a very important enzyme, chitin synthase. Thus, by blocking the transport of N-acetylglucosamine across the epithelial membrane, TFM could therefore act as a general stressor making the insect more susceptible to diseases. This facilitates the entry of pathogenic fungi into the insect through the weakening of their cuticle which accelerates their death (Tunaz and Uygun 2004).