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Candida species resistant to fluconazole have raised concern in the scientific medical community due to high mortality in patients with invasive disease. In developing countries, such as Brazil, fluconazole is the most commonly used antifungal, and alternative treatments are expensive or not readily available. Furthermore, the occurrence of biofilms is common, coupled with their inherent resistance to antifungal therapies and the host's immune system, these microbial communities have contributed to making infections caused by these yeasts an enormous clinical challenge. Therefore, there is an urgent need to develop alternative medicines, which surpass the effectiveness of already used therapies, but which are also effective against biofilms. Therefore, the present study aimed to describe for the first time the antifungal and antibiofilm action of the derivative 2-amino-5,6,7,8-tetrahydro-4 H-cyclohepta[b]thiophene-3-isopropyl carboxylate (2AT) against clinical strains of Candida spp. resistant to fluconazole (FLZ). When determining the minimum inhibitory concentrations (MIC), it was found that the compound has antifungal action at concentrations of 100 to 200 µg/mL, resulting in 100% inhibition of yeast cells. Its synergistic effect with the drug FLZ was also observed. The antibiofilm action of the compound in subinhibitory concentrations was detected, alone and in association with FLZ. Moreover, using scanning electron microscopy, it was observed that the compound 2AT in isolation was capable of causing significant ultrastructural changes in Candida. Additionally, it was also demonstrated that the compound 2AT acts by inducing characteristics compatible with apoptosis in these yeasts, such as chromatin condensation, when visualized by transmission electron microscopy, indicating the possible mechanism of action of this molecule. Furthermore, the compound did not exhibit toxicity in J774 macrophage cells up to a concentration of 4000 µg/mL. In this study, we identify the 2AT derivative as a future alternative for invasive candidiasis therapy, in addition, we highlighted the promise of a strategy combined with fluconazole in combating Candida infections, especially in cases of resistant isolates.
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The gold standard diagnosis of sporotrichosis is the isolation of Sporothrix sp. in culture media, but this is a time-consuming test that is susceptible to contamination and can be affected by the fungal load. Molecular methods such as nested PCR are gaining more ground in the management of several infections as they are tools for the rapid and accurate identification of microorganisms from pure cultures or directly from biological samples. This study aimed to apply a nested PCR molecular protocol for the rapid detection of Sporothrix spp. directly from clinical samples. Thirteen samples-six from skin biopsies, five from skin exudates, and two from conjunctival secretions-were obtained from patients diagnosed with sporotrichosis due to S. brasiliensis. Calmodulin gene sequencing identified all the isolates as S. brasiliensis. Nested PCR was able to detect all the Sporothrix sensu lato directly from clinical samples as well as the CBS 120339 reference strain. The nested PCR protocol stands out as a diagnostic alternative, as it allows the identification of Sporothrix spp. directly from clinical samples without the need for fungal isolation.
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As the prevalence of drug-resistant Candida isolates continues to rise, the imperative for identifying novel compounds to enhance the arsenal of antifungal drugs becomes increasingly critical. Consequently, exploring new treatment strategies, including synthesizing molecular hybrids and applying combination therapy, is essential. For this reason, this study evaluated the efficacy of ten molecular hybrids of aza-bicyclic 2-isoxazoline-acylhydrazone belonging to two series 90 and 91 as possible anti-Candida agents. In addition, we also investigated the interaction between the hybrids and fluconazole, a commonly used antifungal drug. We evaluated the antifungal effect of aza-bicyclic 2-isoxazoline-acylhydrazone hybrid compounds against six Candida spp. strains that target planktonic cells. However, none of these new molecules were inhibitory active at the tested concentrations (2 to 1,024 µg/mL). Moreover, we analyzed the interaction between the ten new hybrid molecules and fluconazole using the checkerboard assay, employing two different methodologies for reading the plate. For this, one isolate fluconazole-resistant was selected. We observed that only one combination, 6-(4-tert-butylbenzoil)-4,5,6,6a-tetrahydro-3a-H-pirrole[3,2-d]isoxazole-3-carboxylic(furan-2-metilidene)-hydrazide (91e) and fluconazole, exhibited a synergistic interaction (FICI range 0.0781 to 0.4739). The combination successfully inhibited the growth of C. albicans CA2 fluconazole-resistant, and no interaction was observed in an isolate susceptible to fluconazole. Additionally, these results emphasize the continued need for research into new compounds and the importance of using combined approaches to increase their activity.
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Antifúngicos , Candida albicans , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Fluconazol , Hidrazonas , Isoxazoles , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Antifúngicos/química , Fluconazol/farmacología , Candida albicans/efectos de los fármacos , Hidrazonas/farmacología , Hidrazonas/química , Isoxazoles/farmacología , Isoxazoles/química , HumanosRESUMEN
Species from Candida parapsilosis complex are frequently found in neonatal candidemia. The antifungal agents to treat this infection are limited and the occurrence of low in vitro susceptibility to echinocandins such as micafungin has been observed. In this context, the chaperone Hsp90 could be a target to reduce resistance. Thus, the objective of this research was to identify isolates from the C. parapsilosis complex and verify the action of Hsp90 inhibitors associated with micafungin. The fungal identification was based on genetic sequencing and mass spectrometry. Minimal inhibitory concentrations were determined by broth microdilution method according to Clinical Laboratory and Standards Institute. The evaluation of the interaction between micafungin with Hsp90 inhibitors was realized using the checkerboard methodology. According to the polyphasic taxonomy, C. parapsilosis sensu stricto was the most frequently identified, followed by C. orthopsilosis and C. metapsilosis, and one isolate of Lodderomyces elongisporus was identified by genetic sequencing. The Hsp90 inhibitor geladanamycin associated with micafungin showed a synergic effect in 31.25% of the isolates, a better result was observed with radicicol, which shows synergic effect in 56.25% tested yeasts. The results obtained demonstrate that blocking Hsp90 could be effective to reduce antifungal resistance to echinocandins.
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Antifúngicos , Candida parapsilosis , Candidemia , Proteínas HSP90 de Choque Térmico , Micafungina , Humanos , Recién Nacido , Antifúngicos/farmacología , Benzoquinonas/farmacología , Candida parapsilosis/efectos de los fármacos , Candida parapsilosis/aislamiento & purificación , Candida parapsilosis/genética , Candidemia/microbiología , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Equinocandinas/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/genética , Lactamas Macrocíclicas/farmacología , Lipopéptidos/farmacología , Micafungina/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
Premature hospitalized neonates have a greater risk for candidemia, however, fungemia due to rare opportunistic yeasts have been recently reported and is associated with high mortality rates. We herein report the first case in Latin America of Lodderomyces elongisporus fungemia in a premature neonate with a fatal outcome.
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Candidemia , Fungemia , Enfermedades del Recién Nacido , Saccharomycetales , Recién Nacido , Humanos , Fungemia/diagnóstico , Fungemia/tratamiento farmacológico , América Latina , Saccharomycetales/genética , Candidemia/tratamiento farmacológico , Levaduras , Antifúngicos/farmacología , Antifúngicos/uso terapéuticoRESUMEN
In this context, the objective of this work was to isolate an alkaline lignin from the leaves of C. ferrea, in addition to investigating different biological activities and its use in the production of releasing tablets in vitro. Initially, the analysis of the composition of the leaves was performed, the contents were: cellulose (33.09 ± 0.3 %), hemicellulose (25.13 ± 0.1 %), lignin (18.29 ± 0.1 %), extractives (17.28 ± 1.0 %) and ash (6.20 ± 0.1 %). The leaves were fractionated to obtain alkaline lignin. The yield of obtaining lignin was 80.12 ± 0.1 %. The obtained lignin was characterized by the techniques: elemental analysis, FTIR, UV/Vis, 2D-NMR, GPC, TGA/DTG, DSC and PY-GC/MS. The results showed that the lignin obtained is of the GSH type, of low molecular weight and thermally stable. The in vitro antioxidant activity was evaluated by different assays promoting results only for DPPH (559.9 ± 0.8 µg/mL) and ABTS (484.1 ± 0.1 µg/mL) being able to promote low antioxidant activity. In addition, it showed low cytotoxicity in normal mammalian cells and promising antitumor and trypanocidal activity. Regarding antimicrobial activity, it was able to inhibit the growth of a strain of Staphylococcus aureus resistant to methicillin, presenting MIC values equal to the standard antibiotic oxacillin. It was also able to inhibit a strain of Candida albicans HAM13 sensitive to fluconazole. In addition, lignin promoted a synergistic effect by promoting a decrease in MIC against these two strains evaluated. Finally, lignin proved to be an excipient with potential for controlled release of antimicrobials.
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The aim of this study was to evaluate the efficacy and non-toxicity of ciclopirox olamine-loaded liposomes against Cryptococcus neoformans clinical isolates. Initially, 24-1 fractional experimental design was carried out to obtain an optimized formulation of liposomes containing CPO (CPO-LipoC), which were then used to prepare stealth liposomes (CPO-LipoS). Liposomal formulations were characterized by their mean size diameter, polydispersity index (PDI), and drug encapsulation efficiency (EE%). Immunosuppressed mice were exposed to CPO-LipoS at 0.5 mg/kg/day for 14 days to verify possible histopathological alterations in the liver and kidneys. Immunosuppressed mice infected with C. neoformans were treated with CPO-LipoS at 0.5 mg/kg/day for 14 days to quantify the fungal burden in spleen, liver, lungs, and brain. CPO-LipoS presented a mean size diameter, PDI, and EE% of 101.4 ± 0.7 nm, 0.307, and 96.4 ± 0.9%, respectively. CPO-LipoS was non-toxic for the liver and kidneys of immunosuppressed mice. At the survival curve, all infected animals submitted to treatment with CPO-LipoS survived until the end of the experiment. Treatment with CPO-LipoS reduced C. neoformans cells in the spleen (59.3 ± 3.4%), liver (75.0 ± 3.6%), lungs (75.7 ± 6.7%), and brain (54.2 ± 3.2%). CPO-LipoS exhibit antifungal activity against C. neoformans, and the encapsulation of CPO into stealth liposomes allows its use as a systemic drug for treating cryptococcosis.
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Criptococosis , Cryptococcus neoformans , Animales , Ratones , Ciclopirox/uso terapéutico , Liposomas , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Criptococosis/tratamiento farmacológico , Criptococosis/microbiologíaRESUMEN
Cryptococcal meningitis is a serious infection of the central nervous system that is predominant in developing countries, caused by fungi of the genus Cryptococcus, and which affects immunosuppressed patients, especially those with HIV. Here, we aim to diagnose and characterize the clinical-epidemiological profile of cryptococcosis in patients admitted to two tertiary public hospitals in northeastern Brazil. The study is divided into three moments: (1) the isolation of fungus and diagnosis from biological samples collected between 2017 and 2019, (2) a description of the clinical and epidemiological characteristics of the patients, and (3) the experimental tests related to an in vitro susceptibility antifungal profile. The species were identified by MALDI-TOF/MS. Among the 100 patients evaluated, 24 (24.5%) were diagnosed with cryptococcosis based on positive culture. Clinical-epidemiological analysis showed a slightly higher prevalence in men between 30 and 39 years. When comparing the date of HIV diagnosis and the development of cryptococcosis, it was observed that 50% received the diagnosis of infection by cryptococcosis after or equal to a period of 12 months from being diagnosed with HIV; the other 50% received it within the first 30 days of the HIV diagnosis. Neurocryptococcosis was the most prevalent clinical form, and, at the time of hospital admission, the most common clinical signs were high fever (75%), intense headache (62.50%), and neck stiffness (33.33%). The cerebrospinal fluid showed 100% sensitivity and positivity for direct examination by India ink, and fungal culture. The mortality rate in this study was 46% (11/24), a lower rate than in the other literature. An antifungigram showed that 20 (83.33%) isolates were susceptible to amphotericin B and 15 (62.5%) to fluconazole. Mass spectrometry identified 100% of the isolates as Cryptococcus neoformans. In Brazil, this infection is not mandatory notifiable. Therefore, although there is little information on the subject, it is obsolete and does not express the reality of the facts, mainly in the northeast region, where this information is insufficient. The data obtained in this research contribute to the epidemiological knowledge of this mycosis in Brazil and will serve as a basis for future globally comparative epidemiological studies.
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Criptococosis , Cryptococcus neoformans , Infecciones por VIH , Masculino , Humanos , Brasil/epidemiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Criptococosis/epidemiología , Criptococosis/complicaciones , Criptococosis/diagnóstico , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiologíaRESUMEN
Candidemia is responsible for substantial morbidity and mortality in neonatal intensive care units and represents a challenge due to the complexity of hospitalized neonates, the deficiency in approved and precise diagnostic techniques, and the increasing number of species resistant to antifungal agents. Thus, the objective of this study was to detect candidemia among neonates evaluating the risk factors, epidemiology, and antifungal susceptibility. Blood samples were obtained from neonates with suspected septicemia, and the mycological diagnosis was based on yeast growth in culture. The fungal taxonomy was based on classic identification, automated system, and proteomic, when necessary molecular tools were used. The in vitro susceptibility tests were performed according to the broth microdilution method from Clinical and Laboratory Standards Institute. Statistical analysis was performed using the R software version R-4.2.2. The prevalence of neonatal candidemia was 10.97%. The major risk factors involved were previous use of parenteral nutrition, exposure to broad-spectrum antibiotics, prematurity, and prior use central venous catheter, but only this last was statistically associated with mortality risk. Species from Candida parapsilosis complex and C. albicans were the most frequent. All isolates were susceptible to amphotericin B, except C. haemulonii that also exhibited elevated MICs to fluconazole. C. parapsilosis complex and C. glabrata exhibit the highest MICs to echinocandins. Considering these data, we emphasize that an effective management strategy to reduce the impact of neonatal candidemia should involve the knowledge of risk factors, rapid and precise mycological diagnostic, and tests of antifungal susceptibility to help in the selection of an appropriate treatment.
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Candidemia , Recién Nacido , Humanos , Candidemia/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida , Brasil/epidemiología , Unidades de Cuidado Intensivo Neonatal , Proteómica , Fluconazol , Farmacorresistencia Fúngica , Factores de Riesgo , Candida glabrata , Candida albicans , Candida parapsilosis , Pruebas de Sensibilidad MicrobianaRESUMEN
Yeasts from the Candida parapsilosis complex are clinically relevant due to their high virulence and pathogenicity potential, such as adherence to epithelial cells and emission of filamentous structures, as well as their low susceptibility to antifungals. D-limonene, a natural compound, emerges as a promising alternative with previously described antibacterial, antiparasitic, and antifungal activity; however, its mechanisms of action and antivirulence activity against C. parapsilosis complex species have not been elucidated. Therefore, in the present study, we aimed to evaluate the antifungal and antivirulence action, as well as the mechanism of action of D-limonene against isolates from this complex. D-limonene exhibited relevant antifungal activity against C. parapsilosis complex yeasts, as well as excellent antivirulence activity by inhibiting yeast morphogenesis and adherence to the human epithelium. Furthermore, the apoptotic mechanism induced by this compound, which is not induced by oxidative stress, represents an important target for the development of new antifungal drugs.
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Antifúngicos , Candida parapsilosis , Humanos , Antifúngicos/farmacología , Virulencia , Limoneno/farmacología , Factores de Virulencia , Pruebas de Sensibilidad Microbiana , Saccharomyces cerevisiaeRESUMEN
BACKGROUND: Opportunistic infections are frequent in people living with the human immunodeficiency virus who either do not have access to antiretroviral therapy (ART) or use it irregularly. Tuberculosis is the most frequent infectious disease in PLHIV and can predispose patients to severe fungal infections with dire consequences. CASE PRESENTATION: We describe the case of a 35-year-old Brazilian man living with human immunodeficiency virus (HIV) for 10 years. He reported no adherence to ART and a history of histoplasmosis with hospitalization for 1 month in a public hospital in Natal, Brazil. The diagnosis was disseminated Mycobacterium tuberculosis infection. He was transferred to the health service in Recife, Brazil, with a worsening condition characterized by daily fevers, dyspnea, pain in the upper and lower limbs, cough, dysphagia, and painful oral lesions suggestive of candidiasis. Lymphocytopenia and high viral loads were found. After screening for infections, the patient was diagnosed with tuberculous pericarditis and esophageal candidiasis caused by Candida tropicalis. The isolated yeasts were identified using the VITEK 2 automated system and matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry. Antifungal microdilution broth tests showed sensitivity to fluconazole, voriconazole, anidulafungin, caspofungin, micafungin, and amphotericin B, with resistance to fluconazole and voriconazole. The patient was treated with COXCIP-4 and amphotericin deoxycholate. At 12 days after admission, the patient developed sepsis of a pulmonary focus with worsening of his respiratory status. Combined therapy with meropenem, vancomycin, and itraconazole was started, with fever recurrence, and he changed to ART and tuberculostatic therapy. The patient remained clinically stable and was discharged with clinical improvement after 30 days of hospitalization. CONCLUSION: Fungal infections should be considered in patients with acquired immunodeficiency syndrome as they contribute to worsening health status. When mycoses are diagnosed early and treated with the appropriate drugs, favorable therapeutic outcomes can be achieved.
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Candidiasis , Esofagitis , Micosis , Pericarditis Tuberculosa , Masculino , Humanos , Adulto , Fluconazol/uso terapéutico , Voriconazol/uso terapéutico , Pericarditis Tuberculosa/complicaciones , Pericarditis Tuberculosa/diagnóstico , Pericarditis Tuberculosa/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Micosis/tratamiento farmacológico , Antifúngicos/uso terapéutico , Esofagitis/tratamiento farmacológico , VIHRESUMEN
(1) Background: Candida is a genus of yeasts with notable pathogenicity and significant ability to develop antimicrobial resistance. Gossypium hirsutum L., a medicinal plant that is traditionally used due to its antimicrobial properties, has demonstrated significant antifungal activity. Therefore, this study investigated the chemical composition and anti-Candida effects of aqueous (AELG) and hydroethanolic (HELG) extracts obtained from the leaves of this plant. (2) Methods: The extracts were chemically characterized by UPLC-QTOF-MS/MS, and their anti-Candida activities were investigated by analyzing cell viability, biofilm production, morphological transition, and enhancement of antifungal resistance. (3) Results: The UPLC-QTOF-MS/MS analysis revealed the presence of twenty-one compounds in both AELG and HELG, highlighting the predominance of flavonoids. The combination of the extracts with fluconazole significantly reduced its IC50 values against Candida albicans INCQS 40006, Candida tropicalis INCQS 40042, and C. tropicalis URM 4262 strains, indicating enhanced antifungal activity. About biofilm production, significant inhibition was observed only for the AELG-treated C. tropicalis URM 4262 strain in comparison with the untreated control. Accordingly, this extract showed more significant inhibitory effects on the morphological transition of the INCQS 40006 and URM 4387 strains of C. albicans (4) Conclusions: Gossypium hirsutum L. presents promising antifungal effects, that may be potentially linked to the combined activity of chemical constituents identified in its extracts.
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Cryptococcosis is an infectious disease of worldwide distribution, caused by encapsulated yeasts belonging to the phylum Basidiomycota. The genus Cryptococcus includes several species distributed around the world. The C. gattii/neoformans species complex is largely responsible for most cases of cryptococcosis. However, clinical series have been published of infections caused by Papiliotrema (Cryptococcus) laurentii and Naganishia albida (Cryptococcus albidus), among other related genera. Here, we examined the pathogenic potential and antifungal susceptibility of C. gattii/neoformans species complex (clades I and II) and related genera (Papiliotrema and Naganishia) isolated from environmental and clinical samples. P. laurentii (clade III), N. liquefasciens/N. albidosimilis (clade IV); and N. adeliensis/N. albida (clade V) strains produced higher levels of phospholipase and hemolysins, whereas the C. gattii/neoformans species complex strains (clades I and II) had markedly thicker capsules, produced more biofilm biomass and melanin, which are known virulence attributes. Interestingly, 40% of C. neoformans strains (clade II) had MICs above the ECV established for this species to amphotericin B. Several non-C. gattii/neoformans species complex (clades III to V) had MICs equal to or above the ECVs established for C. deuterogattii and C. neoformans for all the three antifungal drugs tested. Finally, all the non-C. gattii/neoformans clinical isolates (clades III to V) produced more melanin than the environmental isolates might reflect their particularly enhanced need for melanin during in vivo protection. It is very clear that C. gattii/neoformans species complex (clades I and II) strains, in general, show more similar virulence phenotypes between each other when compared to non-C. gattii/neoformans species complex (clades III to V) isolates. These observations together with the fact that P. laurentii and Naganishia spp. (clades III to V) strains were collected from the outside of a University Hospital, identify features of these yeasts important for environmental and patient colonization and furthermore, define mechanisms for infections with these uncommon pathogens.
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Basidiomycota , Cryptococcus gattii , Cryptococcus neoformans , Antifúngicos/farmacología , Humanos , Virulencia , Factores de VirulenciaRESUMEN
The aim of this preliminary study was to identify microorganisms with antimicrobial resistance profile and biofilm producers in oropharynx of Rupornis magnirostris and Caracara plancus. Six R. magnirostris and six C. plancus maintained in Triage Center for Wild Animals (CETAS) facilities were studied. Coagulase-positive staphylococci (CoPS), enterobacteria, and yeasts were identified by the biochemical analysis or MALDI-TOF mass spectrometry. The resistance profile of the microorganisms was analyzed according to CLSI. The biofilm production was evaluated by Congo red and violet crystal staining methods. Among the 12 birds, 10 presented strains of CoPS and/or enterobacteria with resistance profile, such as methicillin-resistant CoPS (MR-CoPS), vancomycin-resistant CoPS (VR-CoPS), extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL), and Klebsiella pneumoniae carbapenemase- (KPC-) producing bacteria. Regards the fungal analysis, Candida spp., Cryptococcus spp., Rhodotorula mucilaginosa, R. glutinis, and Trichosporon coremiiforme were identified. All the Trichosporon coremiiforme strains were resistant to amphotericin B, as well as all the Rhodotorula mucilaginosa exhibited resistance to fluconazole. Related to the biofilm production, among the 8 CoPS, 27 enterobacteria, and 10 yeasts isolates, 3, 16, and 7 strains were biofilm producers, respectively. Thus, the presence of these microorganisms in birds of prey is worrisome, highlighting its possible influence in the spread of infections in urban centers.
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The Candida parapsilosis complex has been associated with highly refractory infections mainly due to the presence of biofilms. High glucose levels enable the development of this virulence factor which can aggravate the clinical condition of patients with diabetes mellitus, those using parenteral nutrition, with invasive medical device, including others. Combined antifungal therapy, such as azole and cyclooxygenase inhibitors, may be an alternative in such infections since they modulate prostaglandin production favoring the adhesion and development of biofilms. Thus, the present study aimed to evaluate the influence of glucose supplementation in the formation and detection of Candida parapsilosis complex biofilms and to treat them using fluconazole and a cyclooxygenase inhibitor in combination. Protein spectra evaluation allowed the differentiation between species from the complex (score > 2) in our studies. All isolates were able to form active biofilms at different glucose concentrations. In addition, a significant reduction in biofilm formation was observed when fluconazole and acetylsalicylic acid were combined. The ultrastructural analysis presented typical biofilm characteristics by species from the complex. These data support new combined therapies for the treatment of fungal infections, especially with those which are resistant and therapeutic failure is associated with virulence factors.
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Aspirina/farmacología , Biopelículas/efectos de los fármacos , Candida parapsilosis/efectos de los fármacos , Fluconazol/farmacología , Antifúngicos/farmacología , Aspirina/administración & dosificación , Candida parapsilosis/fisiología , Inhibidores de la Ciclooxigenasa/farmacología , Fluconazol/administración & dosificación , Glucosa/metabolismo , Pruebas de Sensibilidad MicrobianaRESUMEN
Sporothrix chilensis is a mild-pathogenical specie of Sporothrix pallida complex, until now, known as restrict to Chile. Herein, we describe the first clinical isolates identified as S. chilensis in Brazil, preserved in the URM Culture Collection, by polyphasic taxonomy, and their respective antifungal profile of this emergent fungus.
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Sporothrix/clasificación , Sporothrix/aislamiento & purificación , Esporotricosis/microbiología , Antifúngicos/farmacología , Brasil , Humanos , Pruebas de Sensibilidad Microbiana , Técnicas de Tipificación Micológica , Análisis de Secuencia de ADN , Sporothrix/genética , Sporothrix/fisiología , Tubulina (Proteína)/genéticaRESUMEN
The objective of this study was to evaluate the effects of nanoparticles (nanospheres and nanocapsules) of the promising antifungal 2-amino-thiophene (6CN10) and 6CN10 complexed with 2-hydroxypropyl-ß-cyclodextrin (6CN10:HP-ß-CD) in vitro and compared with free drug against Candida and Cryptococcus, using a microdilution method to measure susceptibility. The Candida and Cryptococcus clinical strains were identified using phenotypic methods and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). To measure in vitro antifungal susceptibility, we used microdilution trials. Serial drug or nanoparticle dilutions were prepared according to the CLSI M27-A3 guidelines. Anti-biofilm activity was verified for Cryptococcus neoformans. All Candida isolates were sensitive to the free drug (MIC = 41.66-333.33 µg/mL) and were able to grow even at the higher concentration tested for all 6CN10 nanoparticles. However, the Cryptococcus neoformans strains presented MIC values of 0.32-83.33 µg/mL for 6CN10 nanoparticles, and MIC values of 0.1-0.2 µg/mL for 6CN10:HP-ß-CD nanoparticles, i.e., 3333 times more active than the free drug (MIC values 166.66-333.33 µg/mL), and presenting activity greater than that of the reference drug amphotericin B (MIC = 0.5-0.125 µg/mL). 6CN10:HP-ß-CD nanosphere also showed high anti-biofilm potential. The in vitro study showed that the nanoparticles allowed better drug efficiency against Cryptococcus than did the free drug. These results suggest that 6CN10-loaded nanoparticles may become a future alternative for cryptococcosis and candidiasis therapy. In vivo experiments are essential prior to clinical use.