scholarly journals Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 737
Author(s):  
Marina Pekmezovic ◽  
Melina Kalagasidis Krusic ◽  
Ivana Malagurski ◽  
Jelena Milovanovic ◽  
Karolina Stępień ◽  
...  

Novel biodegradable and biocompatible formulations of “old” but “gold” drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form of films (~50 µm). Thermal properties and stability of the materials were not significantly altered by the incorporation of polyenes in mcl-PHA, but polyene containing materials were more hydrophobic. These formulations were tested in vitro against a panel of pathogenic fungi and for antibiofilm properties. The films containing 0.1 to 2 weight % polyenes showed good activity and sustained polyene release for up to 4 days. A PHA monomer, namely 3-hydroxydecanoic acid (C10-OH), was added to the films to achieve an enhanced synergistic effect with polyenes against fungal growth. Mcl-PHA based polyene formulations showed excellent growth inhibitory activity against both Candida yeasts (C. albicans ATCC 1023, C. albicans SC5314 (ATCC MYA-2876), C. parapsilosis ATCC 22019) and filamentous fungi (Aspergillus fumigatus ATCC 13073; Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102). All antifungal PHA film preparations prevented the formation of a C. albicans biofilm, while they were not efficient in eradication of mature biofilms, rendering them suitable for the transdermal application or as coatings of implants.

Microbiology ◽  
2011 ◽  
Vol 157 (8) ◽  
pp. 2348-2356 ◽  
Author(s):  
Sirida Youngchim ◽  
Soraya Pornsuwan ◽  
Joshua D. Nosanchuk ◽  
Wiyada Dankai ◽  
Nongnuch Vanittanakom

Dermatophytes are keratinophilic fungi that are the most common cause of fungal skin infections worldwide. Melanin has been isolated from several important human fungal pathogens, and the polymeric pigment is now recognized as an important virulence determinant. This study investigated whether dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum and Microsporum gypseum, produce melanin or melanin-like compounds in vitro and during infection. Digestion of the pigmented microconidia and macroconidia of dermatophytes with proteolytic enzymes, denaturant and hot concentrated acid yielded dark particles that retained the size and shape of the original fungal cells. Electron spin resonance spectroscopy revealed that particles derived from pigmented conidia contained a stable free radical signal, consistent with the pigments being a melanin. Immunofluorescence analysis demonstrated reactivity of a melanin-binding mAb with the pigmented conidia and hyphae, as well as the isolate particles. Laccase, an enzyme involved in melanization, was detected in the dermatophytes by an agar plate assay using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the substrate. Skin scrapings from patients with dermatophytoses contained septate hyphae and arthrospores that were reactive with the melanin-binding mAb. These findings indicate that dermatophytes can produce melanin or melanin-like compounds in vitro and during infection. Based on what is known about the function of melanin as a virulence factor of other pathogenic fungi, this pigment may have a similar role in the pathogenesis of dermatophytic diseases.


2001 ◽  
Vol 8 (3) ◽  
pp. 165-169 ◽  
Author(s):  
A. Smicka ◽  
V. Buchta ◽  
K. Handlir

Six new N-substituted di- and tributyltin 2-aminoethanethiolates (cysteaminates) have been prepared and characterised by H1, C13 and S119n NMR spectroscopy. All these compounds exhibit a good in vitro antifungal effect against selected types of human pathogenic fungi (Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes) and their activity is comparable with that of some antifungal drugs commonly used in the clinical use like ketoconazole. The structure-activity relationships in these compounds are discussed.


2010 ◽  
Vol 59 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Ildikó Nyilasi ◽  
Sándor Kocsubé ◽  
Miklós Pesti ◽  
Gyöngyi Lukács ◽  
Tamás Papp ◽  
...  

The in vitro antifungal activities of primycin (PN) and various statins against some opportunistic pathogenic fungi were investigated. PN completely inhibited the growth of Candida albicans (MIC 64 μg ml−1) and Candida glabrata (MIC 32 μg ml−1), and was very effective against Paecilomyces variotii (MIC 2 μg ml−1), but had little effect on Aspergillus fumigatus, Aspergillus flavus or Rhizopus oryzae (MICs >64 μg ml−1). The fungi exhibited different degrees of sensitivity to the statins; fluvastatin (FLV) and simvastatin (SIM) exerted potent antifungal activities against a wide variety of clinically important fungal pathogens. Atorvastatin, rosuvastatin and lovastatin (LOV) had a slight effect against all fungal isolates tested, whereas pravastatin was completely ineffective. The in vitro interactions between PN and the different statins were investigated using a standard chequerboard titration method. When PN was combined with FLV, LOV or SIM, both synergistic and additive effects were observed. The extent of inhibition was higher when these compounds were applied together, and the concentrations of PN and the given statin needed to block fungal growth completely could be decreased by several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities was investigated.


2012 ◽  
Vol 3 (1) ◽  
pp. 6 ◽  
Author(s):  
Sunil Kumar Deshmukh ◽  
Shilpa Amit Verekar

The parks of Mumbai are frequently visited by local residents every morning and evening. However, there are no reports on the occurrence of keratinophilic fungi in these areas. The purpose of this research was to study the occurrence of keratinophilic fungi in the public parks of Mumbai. One hundred soil samples were collected from five public parks: Kamla Nehru Park, Powai Garden, CD Deshmukh Garden, Five Gardens and Chota Kashmir. Keratinophilic fungi were isolated by the hair baiting technique using human hair as keratin bait. The cultures were identified using macroand micro-morphological features. Identification was also confirmed by the BLAST search of sequences of the ITS1-5.8S-ITS2 rDNA region against the NCBI/Genbank data and compared with deposited sequences. The ability of these fungi to use human hair was also evaluated by release of protein in liquid media. A total of 75 strains of keratinophilic fungi were recovered from 100 (75.0%) soil samples. The isolated fungi were composed of eleven species of eight genera: <em>Arthrographis kalrae</em>, A<em>uxarthron conjugatum</em>, <em>Chrysosporium indicum</em>, <em>C. queenslandicum</em>, <em>C. zonatum, Gymnascella dankaliensis</em>, <em>G. hyalinospora</em>,<em> Microsporum gypseum</em> (15.0%), <em>Myriodontium keratinophilum</em>, <em>Trichophyton mentagrophytes</em> and <em>Uncinocarpus reesii</em>. These fungi can release 148.8-307.6 μg/mL protein in liquid media when grown on human hair in shake flask culture and also decompose 16.2-38.6% of human hair after four weeks of incubation. Our study indicates that keratinophilic fungi are to be found in the soils of various public parks in Mumbai and that human hair can be a source of pathogenic fungi.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 559
Author(s):  
Tatiana de los Ángeles Mosquera Tayupanta ◽  
Sandra Elizabeth Ayala Valarezo ◽  
Tatiana Alexandra Vasquez Villareal ◽  
María Belén Montaluisa Álvarez

Background: Currently, there is a trend towards using natural and ethnopharmacological species with therapeutic potential. This investigation evaluated the antifungal activity of two species in the Ecuadorian Andes, which are used in treating dermatomycosis: Ambrosia arborescens Mill. (Marco) and Aristeguietia glutinosa Lam. (Matico). Methods: We worked with seven concentrations (100 to 700ppm) of Ambrosia arborescens Mill. extract and ten concentrations (0.5 to 5%) of essential oil (EO) of Aristeguietia glutinosa Lam. on Trichophyton mentagrophytes ATCC 9533, Trichophyton rubrum ATCC 28188, Microsporum canis ATCC 36299 and Candida albicans ATCC 10231. The methodology used was a modified version of the Kirby-Bauer method, using diffusion in agar wells. Results: The Tukey test, after the one-way Anova, determined effective concentrations of EO: 5% for Trichophyton mentagrophytes, 4.5% for Trichophyton rubrum, 5% for Microsporum canis and 2% for Candida albicans. In the extracts, the concentration of 700ppm was used for Trichophyton mentagrophytes, Trichophyton rubrum, and 600ppm for Microsporum canis and Candida albicans. Conclusions: The evaluation of the antifungal activity of the Ambrosia arborescens extract showed inhibition in the studied dermatophytes in each one of the planted concentrations (100 to 700ppm). The evaluation of the antifungal activity of Aristeguietia glutinosa EO showed inhibition in the studied dermatophytes in each of the planted concentrations (0.5 to 5%).


2020 ◽  
Vol 1 (1) ◽  
pp. 33-40
Author(s):  
Renu Jangid ◽  
Tahira vbegum

Plant products have been used as medicines against fungal infectious diseases. In this research antimycotic activity of the leaf extracts of five medicinal plants (Nerium indicum, Catheranthus roseus, Lantana camera, Ziziphus mauritiana) were tested against three dermatophytes (Trichophyton mentagrophytes, Trichophyton rubrum and Microsporum. gypseum). Development of more effective and less toxic antimycotic agents is required for the treatment of dermatophytosis. The plant materials were extracted with methanol, ethanol and diethyl ether solvent to investigate their antimycotic activities in Vitro. Ethanol and methanol extracts of all selected medicinal plants were showed the positive activity against all tested dermatophytes. Diethyl ether extract was showed lowest activity against T. mentagrophytes and T. rubrum and showed moderate activity against M. gypseum. The three dermatophytes differed with regard to their susceptibility to plant extracts.


2021 ◽  
pp. 1-3
Author(s):  
Kapaganty V Chakradhar ◽  
Dilruba Begum ◽  
Ruby Devi N ◽  
Raya Roja

This study was conducted to determine the common isolates causing dermatophytosis and other fungi causing dermatomycosis in patients presenting with skin lesions with or without involvement of hair and nails. A total of 75 patients were included in the study with 86 distinctive clinical lesions, of which Tinea corporis (46.7%,) was the most predominant followed by T. cruris (22.7%), T. unguium (14.7%) with a male to female ratio of 1.3:1. KOH mounts were made from samples and examined for fungal elements and samples were sent to Microbiology laboratory for culture, and identication among them 77.3% were skin scrapings alone and 14.7% were nail clippings along with skin scrapings and 8% were hair samples along with skin scrapings. Most common isolate was Trichophyton rubrum (40%) followed by Trichophyton mentagrophytes (17.3%), Trichophyton tonsurans (9.3%), Microsporum gypseum (4%) and no fungal growth was found in 17.3% of the samples. The study signies the importance of mycological examination in the diagnosis of dermatophytosis.


2015 ◽  
Vol 60 (2) ◽  
pp. 1035-1039 ◽  
Author(s):  
Yuji Tabata ◽  
Naomi Takei-Masuda ◽  
Natsuki Kubota ◽  
Sho Takahata ◽  
Makoto Ohyama ◽  
...  

ABSTRACTFungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate thein vitroantifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity againstTrichophyton rubrumandTrichophyton mentagrophytes(the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50and MIC90of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition ofTrichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation.


2021 ◽  
Vol 22 (9) ◽  
pp. 4324
Author(s):  
Claudiu T. Supuran ◽  
Clemente Capasso

Carbon dioxide (CO2), a vital molecule of the carbon cycle, is a critical component in living organisms’ metabolism, performing functions that lead to the building of compounds fundamental for the life cycle. In all living organisms, the CO2/bicarbonate (HCO3−) balancing is governed by a superfamily of enzymes, known as carbonic anhydrases (CAs, EC 4.2.1.1). CAs catalyze the pivotal physiological reaction, consisting of the reversible hydration of the CO2 to HCO3− and protons. Opportunistic and pathogenic fungi can sense the environmental CO2 levels, which influence their virulence or environmental subsistence traits. The fungal CO2-sensing is directly stimulated by HCO3− produced in a CA-dependent manner, which directly activates adenylyl cyclase (AC) involved in the fungal spore formation. The interference with CA activity may impair fungal growth and virulence, making this approach interesting for designing antifungal drugs with a novel mechanism of action: the inhibition of CAs linked to the CO2/HCO3−/pH chemosensing and signaling. This review reports that sulfonamides and their bioisosteres as well as inorganic anions can inhibit in vitro the β- and α-CAs from the fungi, suggesting how CAs may be considered as a novel “pathogen protein” target of many opportunistic, pathogenic fungi.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhongkai Gu ◽  
Yufan Sun ◽  
Feizhen Wu

Pathogenic fungi are recognized as a progressive threat to humans, particularly those with the immunocompromised condition. The growth of fungi is controlled by several factors, one of which is signaling molecules, such as hydrogen sulfide (H2S), which was traditionally regarded as a toxic gas without physiological function. However, recent studies have revealed that H2S is produced enzymatically and endogenously in several species, where it serves as a gaseous signaling molecule performing a variety of critical biological functions. However, the influence of this endogenous H2S on the biological activities occurring within the pathogenic fungi, such as transcriptomic and phenotypic alternations, has not been elucidated so far. Therefore, the present study was aimed to decipher this concern by utilizing S-propargyl-cysteine (SPRC) as a novel and stable donor of H2S and Saccharomyces cerevisiae as a fungal model. The results revealed that the yeast could produce H2S by catabolizing SPRC, which facilitated the growth of the yeast cells. This implies that the additional intracellularly generated H2S is generated primarily from the enhanced sulfur-amino-acid-biosynthesis pathways and serves to increase the growth rate of the yeast, and presumably the growth of the other fungi as well. In addition, by deciphering the implicated pathways and analyzing the in vitro enzymatic activities, cystathionine-γ-lyase (CYS3) was identified as the enzyme responsible for catabolizing SPRC into H2S in the yeast, which suggested that cystathionine-γ-lyase might play a significant role in the regulation of H2S-related transcriptomic and phenotypic alterations occurring in yeast. These findings provide important information regarding the mechanism underlying the influence of the gaseous signaling molecules such as H2S on fungal growth. In addition, the findings provide a better insight to the in vivo metabolism of H2S-related drugs, which would be useful for the future development of anti-fungal drugs.


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