Amphotericin B (AmB) is one of the most effective antifungal drugs, with a strong, dose-dependent activity against most Candida and Aspergillus species responsible for life-threatening infections. However, AmB is severely toxic, which hinders its broad use. In this proof-of-concept study, we demonstrate that prodrugging AmB considerably decreases AmB toxicity without affecting its fungicidal activity. For this purpose, we modified the AmB structure by attaching a designer phosphate promoiety, thereby switching off its mode of action and preventing its toxic effects. The original fungicidal activity of AmB was then restored upon prodrug activation by host plasma enzymes. These AmB prodrugs showed a safer toxicity profile than commercial AmB deoxycholate in Candida and Aspergillus species and significantly prolonged larval survival of infected Galleria mellonella larvae. Based on these findings, prodrugging toxic antifungals may be a viable strategy for broadening the antifungal arsenal, opening up opportunities for targeted prodrug design.
- MeSH
- amfotericin B * farmakologie MeSH
- antifungální látky * farmakologie chemie chemická syntéza MeSH
- Aspergillus účinky léků MeSH
- Candida účinky léků MeSH
- larva účinky léků MeSH
- mikrobiální testy citlivosti * MeSH
- molekulární struktura MeSH
- můry účinky léků MeSH
- prekurzory léčiv * farmakologie chemie chemická syntéza MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
During a study of the diversity of soilborne fungi from Spain, a strain belonging to the family Chaetomiaceae (Sordariales) was isolated. The multigene phylogenetic inference using five DNA loci showed that this strain represents an undescribed species of the genus Amesia, herein introduced as A. hispanica sp. nov. Investigation of its secondary metabolome led to the isolation of two new derivatives (2 and 3) of the known antifungal antibiotic dactylfungin A (1), together with the known compound cochliodinol (4). The planar structures of 1-4 were determined by ultrahigh performance liquid chromatography coupled with diode array detection and ion mobility tandem mass spectrometry (UHPLC-DAD-IM-MS/MS) and extensive 1D and 2D nuclear magnetic resonance (NMR) spectroscopy after isolation by HPLC. All isolated secondary metabolites were tested for their antimicrobial and cytotoxic activities. Dactylfungin A (1) showed selective and strong antifungal activity against some of the tested human pathogens (Aspergillus fumigatus and Cryptococcus neoformans). The additional hydroxyl group in 2 resulted in the loss of activity against C. neoformans but still retained the inhibition of As. fumigatus in a lower concentration than that of the respective control, without showing any cytotoxic effects. In contrast, 25′′-dehydroxy-dactylfungin A (3) exhibited improved activity against yeasts (Schizosaccharomyces pombe and Rhodotorula glutinis) than 1 and 2, but resulted in the appearance of slight cytotoxicity. The present study exemplifies how even in a well-studied taxonomic group such as the Chaetomiaceae, the investigation of novel taxa still brings chemistry novelty, as demonstrated in this first report of this antibiotic class for chaetomiaceous and sordarialean taxa.
- Publikační typ
- časopisecké články MeSH
This article reports the first verified cases of infection by Trichophyton bullosum in Africa since the description of the fungus, isolated in 1933 from the coat of horses in Tunisia and Mali. We found the fungus in cutaneous samples obtained from donkeys suffering from severe dermatitis with areas of alopecia and scaling in the surroundings of Cairo (Egypt). Fungal elements (arthroconidia and hyphae) were seen at the microscopy of material collected by skin scraping and digested in NaOH. Fungal colonies grown on various culture media were identified through PCR and sequencing of the ITS rDNA region. Since the original report in Africa and the Middle East, only a few cases have been reported thus far in humans in France and two cases in horses in the Czech Republic and Japan. Trichophyton bullosum seems thus an infrequent cause of dermatophytosis. However, the actual prevalence of this pathogen may be underestimated due to the similarity with T. verrucosum, a predominant cause of infection in cattle, occasionally found on horses and donkeys. Indeed, the two fungi can be distinguished only via molecular methods, which are poorly employed in epidemiological studies on equine and bovine dermatophytosis. The present study results add to our knowledge on the ecology of this poorly explored dermatophyte, supporting the concept that equines are the primary hosts of T. bullosum and confirming the presence of this pathogen in Africa. At the same time, these are the first unequivocally documented infections in donkeys due to T. bullosum.
- MeSH
- Arthrodermataceae * genetika MeSH
- Equidae MeSH
- koně MeSH
- skot MeSH
- tinea * epidemiologie mikrobiologie veterinární MeSH
- Trichophyton genetika MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- severní Afrika MeSH
Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human well-being. In the current paper, we highlight some important discoveries and developments in applied mycology and interdisciplinary Life Science research. These examples concern recently introduced drugs for the treatment of infections and neurological diseases; application of -OMICS techniques and genetic tools in medical mycology and the regulation of mycotoxin production; as well as some highlights of mushroom cultivaton in Asia. Examples for new diagnostic tools in medical mycology and the exploitation of new candidates for therapeutic drugs, are also given. In addition, two entries illustrating the latest developments in the use of fungi for biodegradation and fungal biomaterial production are provided. Some other areas where there have been and/or will be significant developments are also included. It is our hope that this paper will help realise the importance of fungi as a potential industrial resource and see the next two decades bring forward many new fungal and fungus-derived products.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Species from the Trichophyton benhamiae complex are mostly zoophilic dermatophytes which cause inflammatory dermatophytosis in animals and humans worldwide. OBJECTIVES: This study was purposed to (a) to identify 169 reference and clinical dermatophyte strains from the T benhamiae complex species by molecular method and adhering to the newest taxonomy in the complex (b) to evaluate the in vitro antifungal susceptibility profile of these strains against eight common and new antifungal agents that may be used for the treatment of dermatophytosis. METHODS: All isolates, mainly originated from Europe but also from Iran, Japan and USA, were subjected to ITS-rDNA sequencing. The in vitro antifungal susceptibility profiles of eight common and new antifungal drugs against the isolates were determined by CLSI M38-A2 protocol and according to microdilution method. RESULTS: Based on the ITS-rDNA sequencing, T benhamiae was the dominant species (n = 102), followed by T europaeum (n = 29), T erinacei (n = 23), T japonicum (n = 10), Trichophyton sp (n = 4) and T eriotrephon (n = 1). MIC ranges across all isolates were as follows: luliconazole: 0.0002-0.002 µg/ml, terbinafine: 0.008-0.125 µg/ml, efinaconazole: 0.008-0.125 µg/ml, ciclopirox olamine: 0.03-0.5 µg/ml, itraconazole: 0.06-2 µg/ml, griseofulvin: 0.25-4 µg/ml, amorolfine hydrochloride: 0.125-4 µg/ml and tavaborole: 1-16 µg/ml. CONCLUSION: Luliconazole, efinaconazole and terbinafine were the most potent antifungals against T benhamiae complex isolates, regardless of the geographic locations where strains were isolated. These data might help dermatologists to develop effective therapies for successful treatment of infections due to T benhamiae complex species.
- MeSH
- antifungální látky farmakologie terapeutické užití MeSH
- Arthrodermataceae klasifikace účinky léků genetika izolace a purifikace MeSH
- lidé MeSH
- tinea farmakoterapie mikrobiologie MeSH
- zoonózy farmakoterapie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Írán MeSH
- Japonsko MeSH
- Spojené státy americké MeSH
The rising number of European hedgehogs (Erinaceus europaeus) admitted every year to wildlife rehabilitation centres might be a source of concern to animal and public health since transmissible diseases, such as dermatophytosis, can be easily disseminated. This study seeks to evaluate the frequency of dermatophyte detection in hedgehogs admitted to a wildlife rehabilitation centre located near Paris, France, and to assess the risk of contamination in the centre in order to adapt prevention measures. A longitudinal cohort study was performed on 412 hedgehogs hosted at the Wildlife Animal Hospital of the Veterinary College of Alfort from January to December 2016. Animals were sampled once a month for fungal culture. Dermatophyte colonies were obtained from 174 out of 686 skin samples (25.4%). Besides Trichophyton erinacei, Trichophyton mentagrophytes and Nannizzia gypsea were also found. Dermatophyte detection seemed to be associated with the presence of skin lesions, while more than one-third of T. erinacei-positive animals were asymptomatic carriers. Healing required several months of treatment with topical and systemic azoles, but dermatophytosis did not seem to reduce the probability of release. Daily disinfection procedures and early detection and treatment of infected and asymptomatic carriers succeeded in limiting dermatophyte transmission between hedgehogs and humans.
- MeSH
- divoká zvířata MeSH
- ježkovití MeSH
- kontrola infekčních nemocí MeSH
- lidé MeSH
- longitudinální studie MeSH
- mykologické určovací techniky metody MeSH
- nemocnice veterinární MeSH
- rizikové faktory MeSH
- tinea * přenos veterinární MeSH
- Trichophyton izolace a purifikace MeSH
- záchranná práce MeSH
- zoonózy * přenos prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Francie MeSH
Zoophilic dermatophytes are frequently responsible for superficial mycoses in mammals worldwide. They comprise approximately ten specialized parasitic fungi belonging to genera Trichophyton and Microsporum. Due to contagious nature of the disease, the majority of species possess potential to cause outbreaks at least in their principal host(s) and at the same time have the capability to infect a wide spectrum of mammals, including humans. The purpose of this chapter is to trace the current changes in the epidemiology of animal-infecting dermatophytes that show large geographic differences and dynamically alter over time. Emphasis is given not only to the most important and widespread dermatophyte species representing global issue for both animal and human medicine (Microsporum canis, Trichophyton mentagrophytes, and T. verrucosum) but also to newly emerging pathogens such as T. benhamiae, an agent of epidemic dermatophytosis in Europe frequently affecting guinea pigs and their breeders or owners. The methods for identification and molecular typing of dermatophytes are summarized due to their importance for outbreak detection and epidemiological surveillance. Strategies for management and prevention of outbreaks are also presented.
Zoofilní dermatofyty jsou nejdůležitějšími původci povrchových mykóz u domácích a hospodářských zvířat, z nichž jsou často přenášeny na člověka. Tato skupina zahrnuje přibližně deset specializovaných parazitických hub, které náleží do rodů Trichophyton a Microsporum. Zatímco u zvířat mají infekce často mírný až asymptomatický průběh, při nákaze člověka se typicky projevují jako silně zánětlivé infekce kůže nebo kštice. Nejčastěji postiženou skupinou jsou děti. Cílem tohoto sdělení je podat ucelený mezioborový přehled o klinickém obraze a diagnostice těchto infekcí u člověka i domácích zvířat, a také o hlavních původcích a jejich prevalenci u zvířat, což jsou základní předpoklady nutné k pochopení dynamiky přenosu na člověka a epidemiologické situace u nás i ve světě. Samostatné podkapitoly jsou věnovány léčbě infekcí u člověka a prevenci šíření zoonotických nákaz. Dále je prezentována analýza pětiletých epidemiologických dat, která zahrnuje 2 361 případů tiney corporis (1 004 zoonotického původu) a 79 případů tiney capitis (60 zoonotických) u českých pacientů.
Zoophilic dermatophytes are the most important agents of the superficial mycoses in domestic and farm animals, and are often transmitted to humans. This group includes approximately ten specialized parasitic fungi belonging to the genera Trichophyton and Microsporum. While infections in animals have often mild symptoms or are asymptomatic, human infections typically manifest as highly inflammatory infections of skin or hairy parts of the head. The children are the most frequently affected group. The aim of this review is to provide a comprehensive interdisciplinary overview of the clinical picture and diagnostic methods of these infections in human and domestic animals, and to summarize available data on the main causal agents and their prevalence in animals. This knowledge is essential for understanding the dynamic of the disease transmission and the local and global epidemiological situation. Separate subchapters are focused on treatment of zoonotic infections and prevention of their spread. An epidemiological analysis of 2361 tinea corporis cases (1004 of zoonotic origin) and 79 tinea capitis cases (60 zoonotic) diagnosed during five-year study in Czech patients is presented.
- Klíčová slova
- zoofilní dermatofyty,
- MeSH
- lidé MeSH
- Microsporum MeSH
- tinea capitis diagnóza epidemiologie terapie MeSH
- tinea * diagnóza epidemiologie terapie MeSH
- Trichophyton MeSH
- zoonózy * diagnóza epidemiologie přenos MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
Uvádíme pět kazuistik kožních mykotických infekcí typu tinea faciei a tinea corporis u čtyř mladých žen a chlapce vyvolaných zoofilním druhem Trichophyton erinacei. Všichni pacienti doma chovali ježka bělobřichého (Atelerix albiventris) a také shodně uvedli, že chovaní ježci neměli žádné viditelné klinické projevy infekce. Jedná se o první detailně zdokumentované případy v České republice. Ložisko infekce na obličeji první pacientky bylo nejprve léčeno lokálně ciklopiroxolaminem s regresí nálezu, následně byla terapie doplněna o systémově podaný terbinafin a úspěšně vyléčena. Celkem tři pacienti se dostavili s lézemi na předloktí a byli ve dvou případech úspěšně léčeni systémově podaným terbinafinem, nebo lokální aplikací ciklopiroxolaminu; údaje o zbývajícím případu jsou neúplné. Pátý pacient s lézí na boku byl nejprve léčen kombinací lokálního ciklopiroxolaminu a kyseliny fusidové a později z důvodu znovuobjevení infekce došlo k vyléčení po aplikaci krému s ekonazolem. Trichophyton erinacei je poměrně vzácným původcem dermatofytóz člověka, obvykle ve spojitosti s kontaktem pacienta s ježky. Vzhledem k morfologické podobnosti s druhem T. interdigitale je možné tyto druhy v laboratoři zaměnit, čímž unikne skutečný zdroj infekce a může docházet k jejímu dalšímu šíření. Ověření identifikace pomocí molekulárních metod, například sekvenací oblasti ITS rDNA, která byla použita v této práci, je tedy velmi žádoucí.
We report five cases of tinea faciei and tinea corporis in four young women and a boy, caused by zoophilic species Trichophyton erinacei. All patients kept hedgehogs (Atelerix albiventris) at home and they consistently stated that animals did not show any visible signs of the infection. These are the first cases in the Czech Republic described in detail. Facial lesion of the 1st patient was treated with ciclopiroxolamine at the beginning with a visible regression and subsequently, the therapy was supplemented with systemic terbinafine. In total, three patients presented with lesions on the forearm, two of them were successfully treated by systemic terbinafine and local ciclopiroxolamine, respectively; information about the remaining case are incomplete. Fifth patient was initially treated by combination of local ciclopiroxolamine and acidum fusidicum; because of the relaps of the infection, the therapy was changed to econazol cream with good clinical effect. Trichophyton erinacei is a rare cause of human dermatophytosis, usually in connection with contact of the patient with a hedgehog. Due to the morphological similarity with the T. interdigitale, these strains can be easily confused in the laboratory. This may lead to the misidentification of the infection source and its further spread. Verification of identification using molecular methods, such as the sequencing of ITS rDNA used in this work, is therefore highly desirable.
- Klíčová slova
- Atelerix albiventris, tinea faciei, tinea corporis, ježek bělobřichý,
- MeSH
- ciklopirox terapeutické užití MeSH
- dítě MeSH
- ježkovití MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- přenos infekční nemoci MeSH
- terbinafin terapeutické užití MeSH
- tinea * diagnóza terapie MeSH
- Trichophyton MeSH
- výsledek terapie MeSH
- zoonózy * diagnóza přenos terapie MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- kazuistiky MeSH
