The primary objective of this work was to evaluate the capability of curcumin, a natural compound found in the Curcuma longa plant, to sensitize a clinical isolate of Candida albicans, which was found to have a high resistance to fluconazole. In addition, we assessed whether the resistance of this isolate was the result of the existence of efflux pumps, which could confer a multiple drug resistance phenotype. To evaluate azole resistance, we used the Clinical Laboratory Standard Institute (CLSI) MIC assays procedures with minor modifications. For evaluation of synergistic interaction of curcumin and fluconazole, checkerboard experiments were employed. Nile red and Rhodamine 6G accumulation assays were used to evaluate efflux pump activity. Curcumin was found to have a great capability to inhibit fluconazole resistance of the isolate of C. albicans. It was capable of restoring its sensitivity to this azole when used at 11 μM. Analysis with different azoles and the two indicated dyes showed that an efflux pump could be acting and contributing to the resistance of this isolate to fluconazole. The results suggest that a major facilitator superfamily (MFS) transporter might be involved in this process.
Analyses of essential oils obtained from fresh and dried leaves and inflorescences of Piper clausenianum were performed using GC-FID, GC-MS and NMR techniques. Forty compounds were detected for these four oils with the total of identified constituents ranging from 88.7% for the dried inflorescences to 97.7% for the dried leaves. Sesquiterpenes were the main constituents in the volatile fraction from leaves with a high percentage of (E)-nerolidol (up to 83%). However, monoterpenes were identified in greater amount in the inflorescences, with linalool percentages from 50% up. The essential oils from fresh leaves and inflorescences were submitted to anti-parasitic activity against a strain of Leishmania amazonensis. Both samples showed biological activity, but the essential oil from P. claussenianum fresh leaves, which was rich in (E)-nerolidol, showed effective growth inhibition of L. amazonensis due to the high percentage of this metabolite in the mixture.
Candidiasis is a major opportunistic fungal infection in humans, and its incidence has increased steadily over the last two decades. Candida albicans, the main species of the genus, has a large arsenal of virulence attributes that contribute to successful infections, such as dimorphism and biofilm formation. The adverse effects of eukaryotic antimicrobial therapies associated with an increase in resistance to the compounds presently available have boosted efforts to improve the therapeutic arsenal against candidiasis with a newer and cheaper range of drugs. In this study, a novel nerolidol-rich essential oil (EO) derived from Piper claussenianum (Miq.) C. DC., Piperaceae, was tested on the growth, transition (yeast to hyphae), formation and stability of biofilms produced by C. albicans. Both inflorescence and leaf EOs were evaluated and revealed MIC values ranging from 0.04 to 0.1 % and 0.2 to 1.26 %, respectively. Furthermore, leaf EO managed to downregulate the yeast-to-hyphae transition by 81 %, as well as reducing biofilm formation by about 30 and 50 % after incubation for 24 and 48 h, respectively. The EO was also able to reduce the viability of pre-formed biofilm by 63.9 %. Finally, the association between the leaf EO and fluconazole was evaluated and revealed an interesting synergistic effect. Taken together, these results demonstrate that this novel compound could be a promising agent and could reinforce the arsenal of therapeutic alternatives for the treatment of candidiasis. Furthermore, it may represent a novel and natural source of nerolidol, which could be of interest pharmaceutically.
The genital localized myiasis is a rare zooparasitic dermatosis. This case reported to a penile myiasis by Dermatobia hominis larvae in a 62 year-old man, who is a retired military official from São Gonçalo city, Rio de Janeiro state, Brazil. This patient was guided to the sexually transmitted diseases (STD) clinic from Universidade Federal Fluminense (UFF) by professionals from a urology outpatient clinic of a public hospital from Rio de Janeiro state. The exam showed a 2 cm diameter nodular lesion with a hyperemic area in the glands penis that had arisen 20 days before the exam. It evolved in a favorable way after larvae removal, through previous local anesthesia and slight pressure in lesion's base with the extraction of the larvae. Penile myiasis is not a very frequent situation, although it must be considered as an option in differential diagnosis of genital infectious diseases, even among people of low economical level, as in the case presented.
Leishmaniasis is one of the most neglected tropical diseases, representing a group of parasitic diseases worldwide spread, occurring in 88 tropical and subtropical countries. Approximately 350 million people live in areas of active transmission of leishmaniasis, with about 1-2 million estimated new cases occurring every year. More than 90% of the cutaneous cases appear in developing countries. Efforts to improve the therapeutic arsenal against leishmaniasis have led to the search for new and cheap range of drugs. In this study, the nerolidol-rich essential oil from Piper claussenianum (Miq.) C. DC., Piperaceae, was assayed on arginase activity of Leishmania amazonensis. The effect of this essential oil on arginase activity levels showed an enzyme inhibition of 62.2%. This result stimulates the scientific interest about the potential value of this plant species on neglected diseases as potential new natural product source of pharmacological interest for the treatment of leishmaniasis.
Candida species are fungal pathogens known to cause a wide spectrum of diseases, and Candida albicans and Candida glabrata are the most common associated with invasive infections. A concerning aspect of invasive candidiasis is the emergence of resistant isolates, especially those highly resistant to fluconazole, the first choice of treatment for these infections. Fungal sphingolipids have been considered a potential target for new therapeutic approaches and some inhibitors have already been tested against pathogenic fungi. The present study therefore aimed to evaluate the action of two sphingolipid synthesis inhibitors, aureobasidin A and myriocin, against different C. albicans and C. glabrata strains, including clinical isolates resistant to fluconazole. Susceptibility tests of aureobasidin A and myriocin were performed using CLSI protocols, and their interaction with fluconazole was evaluated by a checkerboard protocol. All Candida strains tested were sensitive to both inhibitors. Regarding the evaluation of drug interaction, both aureobasidin A and myriocin were synergic with fluconazole, demonstrating that sphingolipid synthesis inhibition could enhance the effect of fluconazole. Thus, these results suggest that sphingolipid inhibitors in conjunction with fluconazole could be useful for treating candidiasis cases, especially those caused by fluconazole resistant isolates.
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