Antifungal effect of (R) and (S)-citronellal enantiomers and their predictive mechanism of action on Candida albicans from voriconazole-resistant onychomycoses / Efeito antifúngico dos enantiômeros (R) e (S)-citronelal e seu mecanismo de ação preditivo sobre Candida albicans de onicomicoses resistentes ao voriconazol

Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-ß-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

A onicomicose é a doença mais comum que afeta a unidade ungueal e representa pelo menos 50% de todas as doenças ungueais. Além disso, a Candida albicans é responsável por aproximadamente 70% das onicomicoses causadas por leveduras. Nesse estudo, foi investigado o efeito antifúngico dos enantiômeros (R) e (S)-citronelal, bem como seu mecanismo de ação preditivo sobre C. albicans de onicomicoses resistentes ao voriconazol. Para este propósito, foram aplicadas técnicas in vitro de microdiluição em caldo e docking molecular de forma preditiva e complementar para os mecanismos de ação. Os principais resultados deste estudo indicam que C. albicans foi resistente ao voriconazol e sensível aos enantiômeros (R) e (S)-citronelal na dose de 256 e 32 µg/mL respectivamente. Além disso, houve aumento da concentração inibitória mínima (CIM) dos enantiômeros na presença do sorbitol e do ergosterol, indicando que estas moléculas possivelmente afetem a integridade da parede e da membrana celular de C. albicans. O docking molecular com proteínas chave da biossíntese e manutenção da parede celular e da membrana plasmática fúngica, demonstraram a possibilidade do (R) e (S)-citronelal interagir com duas importantes enzimas: 1,3-ß-glucan sintase e lanosterol 14α-demetilase. Portanto, os achados desse estudo indicam que os enantiômeros (R) e (S)-citronelal são fungicidas sobre C. albicans de onicomicoses e provavelmente essas substâncias causem danos a parede e a membrana celular desses microrganismos possivelmente por interagir com as enzimas da biossíntese destas estruturas fúngicas.

Onychomycosis caused by Malassezia pachydermatis in a dog

Background: Malassezia species are commensal skin organisms of warm-blooded vertebrates that can act as opportunisticpathogens. Malassezia pachydermatis is of importance in both veterinary and human medicine. Recognised initially ascauses of infection of the skin, they are now known to be superficial commensals as well as potential causes of infections indomestic animals and more serious human conditions such as fungemia. They have also been implicated in the pathogenesisof allergic and other inflammatory diseases. Onychomycosis is defined as fungal infection of the claw (nail disease) causedby dermatophytes (Microsporum and Trichophyton genus), non-dermatophyte molds (hyaline and dematiaceous) and/oryeasts. The objective of this work was to report a case of canine onychomycosis by Malassezia pachydermatis based onreference standard diagnostics of this pathology.Case: A 9-year-old male West Highland White Terrier presented history of claw abnormality: brown staining and partlybrittle. The dog has no apparent history of trauma on the affected claw and no skin disease was reported. Direct examinationof claw was performed using the tape strip technique revealed Malassezia organisms. Nail fragments were cultured ontoSabouraud Dextrose Agar with Chloramphenicol and Cycloheximide. After 10 days of incubation (32ºC) nail fragmentsallowed the isolation of pure colonies of Malassezia pachydermatis. The histopathological evaluation was performed bySector of Veterinary Clinical Pathology, Faculdade de Veterinária (FAVET/UFRGS) and fungal infection due to Malasseziapachydermatis was confirmed by histopathologic examination (Hematoxylin and eosin and Grocott’s methenamine silverstain) of the nail, that revealed abundant yeasts (blastoconidia).Discussion: Fungal infection of the skin, hair and nails are common and are primary caused by the dermatophyte molds.Non-dermatophyte molds isolated from nails...

Onychomycosis caused by Malassezia pachydermatis in a dog

Background: Malassezia species are commensal skin organisms of warm-blooded vertebrates that can act as opportunisticpathogens. Malassezia pachydermatis is of importance in both veterinary and human medicine. Recognised initially ascauses of infection of the skin, they are now known to be superficial commensals as well as potential causes of infections indomestic animals and more serious human conditions such as fungemia. They have also been implicated in the pathogenesisof allergic and other inflammatory diseases. Onychomycosis is defined as fungal infection of the claw (nail disease) causedby dermatophytes (Microsporum and Trichophyton genus), non-dermatophyte molds (hyaline and dematiaceous) and/oryeasts. The objective of this work was to report a case of canine onychomycosis by Malassezia pachydermatis based onreference standard diagnostics of this pathology.Case: A 9-year-old male West Highland White Terrier presented history of claw abnormality: brown staining and partlybrittle. The dog has no apparent history of trauma on the affected claw and no skin disease was reported. Direct examinationof claw was performed using the tape strip technique revealed Malassezia organisms. Nail fragments were cultured ontoSabouraud Dextrose Agar with Chloramphenicol and Cycloheximide. After 10 days of incubation (32ºC) nail fragmentsallowed the isolation of pure colonies of Malassezia pachydermatis. The histopathological evaluation was performed bySector of Veterinary Clinical Pathology, Faculdade de Veterinária (FAVET/UFRGS) and fungal infection due to Malasseziapachydermatis was confirmed by histopathologic examination (Hematoxylin and eosin and Grocotts methenamine silverstain) of the nail, that revealed abundant yeasts (blastoconidia).Discussion: Fungal infection of the skin, hair and nails are common and are primary caused by the dermatophyte molds.Non-dermatophyte molds isolated from nails...(AU)

In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis

Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a-4f) and p-hydroxybenzoic acid (9a-9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b-4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312 µg/mL). On the other hand, the amide series (9a-9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C-11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.(AU)

Descriptive study of onychomycosis in a hospital in São Paulo

Onychomychosis, a nail fungus infection is the most frequent nail ailment, constituting about half of all nail disorders. It can be caused by dermatophytes, non-dermatophytes, yeasts and Prothoteca spp. Methods include 5407 samples of patients with suspected onychomycosis, studied from January 2002 to December 2006, by direct mycological examination and fungi culture. The diagnosis of onychomycosis was confirmed in samples from 3822 direct mycological and/or culture positive. The diagnosis was established by culture for fungi. Among the 1.428 identified agents, the dermatophytes were responsible for 68.6% (N = 980) of cases, followed by yeasts with 27.6% (N = 394), non-dermatophytes fungi with 2.2% (N = 31), Prothoteca spp with 0.1% (N = 2), and associations with 1.5% (N = 22). Females were more affected, with 66% (N = 2527) of cases, and the most affected age group ranged from 31 to 60 years of age (median 47 years). Fungal microbiota is often changed in the world, both quantitatively and qualitatively, and is affected by several environmental factors. Thus, the periodic review of the composition of this microbiota is important to evaluate the epidemiology and thus proportion a better therapeutic response.(AU)