Antiretroviral drugs saquinavir and ritonavir reduce inhibitory concentration values of itraconazole against Histoplasma capsulatum strains in vitro

Recent studies have shown that some drugs that are not routinely used to treat fungal infections have antifungal activity, such as protease inhibitor antiretroviral drugs. This study investigated the in vitro susceptibility of Histoplasma capsulatum var. capsulatum to saquinavir and ritonavir, and its combination with the antifungal itraconazole. The susceptibility assay was performed according to Clinical and Laboratory Standards Institute guidelines. All strains were inhibited by the protease inhibitor antiretroviral drugs. Saquinavir showed minimum inhibitory concentrations ranging from 0.125 to 1 mu g mL(-1) for both phases, and ritonavir presented minimum inhibitory concentrations ranging from 0.0312 to 4 mu g mL(-1) and from 0.0625 to 1 mu g mL(-1) for filamentous and yeast phase, respectively. Concerning the anti fungal itraconazole, the minimum inhibitory concentration values ranged from 0.0019 to 0.125 mu g mL(-1) and from 0.0039 to 0.0312 mu g mL(-1) for the filamentous and yeast phase, respectively. The combination of saquinavir or ritonavir with itraconazole was synergistic against H. capsulatum, with a significant reduction in the minimum inhibitory concentrations of both drugs against the strains (p < 0.05). These data show an important in vitro synergy between protease inhibitors and itraconazole against the fungus H. capsulatum. (C) 2016 Published by Elsevier Editora Ltda.CNPqCAPESUniv Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Fortaleza, CE, BrazilUniv Fed Ceara, Postgrad Program Med Sci, Fortaleza, CE, BrazilUniv Estadual Ceara UECE, Postgrad Program Vet Sci, Fortaleza, CE, BrazilUniv Fed Ceara, Dept Stat & Appl Math, Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilHosp Sao Jose, Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilCNPq: 303396/2014-8CNPq: 552161/2011-0CAPES: AE1 - 0052-000630100/11Web of Scienc

Atividade moduladora de extratos etanólico e hexânico de raiz de Costus cf. arabicus sobre drogas antimicrobianas

The bacterium Escherichia coli is known to produce enterotoxins causing diarrheal diseases. Some species of Staphylococcus are recognized as etiological agents of many animal and human opportunistic infections. Pseudomonas aeruginosa is the main cause of nosocomial infections, mainly affecting immunocompromised patients. Candidiasis is the most frequent opportunistic mycosis, frequently caused by Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei. Medicinal plants have been the source of many remedies used in the clinical practice. In this study, the hexane and methanol extracts of Costus cf. arabicus were assayed to the antibacterial activity alone or associated with aminoglycosides and antifungal drugs. Synergism of the ethanol and hexane were verified by the microdilution method. A synergistic effect of the two extracts combined with the aminoglycosides and antifungal agents was demonstrated. It is therefore suggested that the extracts from Costus cf. arabicus could be used as a source of natural products with resistance-modifying antimicrobial activity, providing a new mechanism against the problem of bacterial and fungal resistance to drugs.A bactéria Escherichia coli é conhecida por produzir enterotoxinas capazes de causar diarréia. Algumas espécies de Staphylococcus são agentes etiológicos de muitas infecções oportunistas em animais e humanos. Pseudomonas aeruginosa é a principal causa de infecções hospitalares, acometendo principalmente pacientes imunocomprometidos. Candidíase é a micose oportunista mais comum, muitas vezes causada por Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata e C. krusei. As plantas medicinais têm sido a fonte de muitos remédios tradicionais aplicados na prática clínica. Neste trabalho, os extratos hexânico e etanólico de Costus cf. arabicus foram testados quanto a sua atividade antibacteriana de forma isolada e em combinação com aminoglicosídeos e antifúngicos. O sinergismo dos extratos etanólico e hexânico foi verificado pelo método de microdiluição. Foi observado um efeito sinérgico de ambos os extratos quando combinados com os aminoglicosideos e antifúngicos. Sugere-se, portanto, que os extratos de Costus cf. arabicus poderiam ser usados como uma fonte de produtos naturais com atividade modificadora de resistência a drogas antimicrobianas, fornecendo um novo mecanismo contra o problema da resistência bacteriana e fúngica a drogas

Terpinen-4-ol, tyrosol, and beta-lapachone as potential antifungals against dimorphic fungi

This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and beta-lapachone against strains of Coccidioides posadasii in filamentous phase (n=22) and Histoplasma capsulatum in both filamentous (n=40) and yeast phases (n=13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 mu g/mL, 20-2860 mu g/mL, and 40-1420 mu g/mL, respectively for terpinen-4-ol250-4000 mu g/mL, 30-2000 mu g/mL, and 10-1000 mu g/mL, respectively, for tyrosoland 0.48-7.8 mu g/mL, 0.25-16 mu g/mL, and 0.125-4 mu g/mL, respectively for p-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules. (C) 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Ceara, Postgrad Program Med Microbiol, Specialized Med Mycol Ctr, Fortaleza, Ceara, BrazilUniv Fed Ceara, Postgrad Program Med Sci, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Cellular Biol Div, Sao Paulo, SP, BrazilUniv Fed Ceara, Dept Stat & Appl Math, Fortaleza, Ceara, BrazilChristus Coll Unichristus, Sch Med, Fortaleza, Ceara, BrazilUniv Estadual Ceara, Postgrad Program Vet Sci, Fortaleza, Ceara, BrazilUniversidade Federal de São Paulo (UNIFESP), Department of Microbiology, Immunology and Parasitology, Cellular Biology Division, São Paulo, SP, BrazilCNPq: 303396/2014-8CNPq: 552161/2011-0CAPES: AE1-0052-000630100/11Web of Scienc

Promethazine improves antibiotic efficacy and disrupts biofilms of <i>Burkholderia pseudomallei</i>

<p>Efflux pumps are important defense mechanisms against antimicrobial drugs and maintenance of <i>Burkholderia pseudomallei</i> biofilms. This study evaluated the effect of the efflux pump inhibitor promethazine on the structure and antimicrobial susceptibility of <i>B</i>. <i>pseudomallei</i> biofilms. Susceptibility of planktonic cells and biofilms to promethazine alone and combined with antimicrobials was assessed by the broth microdilution test and biofilm metabolic activity was determined with resazurin. The effect of promethazine on 48 h-grown biofilms was also evaluated through confocal and electronic microscopy. The minimum inhibitory concentration (MIC) of promethazine was 780 mg l⁻¹, while the minimum biofilm elimination concentration (MBEC) was 780–3,120 mg l⁻¹. Promethazine reduced the MIC values for erythromycin, trimethoprim/sulfamethoxazole, gentamicin and ciprofloxacin and reduced the MBEC values for all tested drugs (<i>p</i><0.05). Microscopic analyses demonstrated that promethazine altered the biofilm structure of <i>B</i>. <i>pseudomallei</i>, even at subinhibitory concentrations, possibly facilitating antibiotic penetration. Promethazine improves antibiotics efficacy against <i>B. pseudomallei</i> biofilms, by disrupting biofilm structure.</p

Yeast microbiota of natural cavities of manatees (Trichechus inunguis and T. manatus) in Brazil and its relevance for animal health and management in captivity

The aim of this study was to characterize the yeast microbiota of natural cavities of manatees kept in captivity in Brazil. Sterile swabs from the oral cavity, nostrils, genital opening and rectum of 50 Trichechus inunguis and 26 T. manatus were collected. The samples were plated on Sabouraud agar with chloramphenicol and incubated at 25 °C for five days. The yeasts isolated were phenotypically identified by biochemical and micromorphological tests. Overall, 141 strains were isolated, of which 112 were from T. inunguis (Candida albicans, C. parapsilosis sensu stricto, C. orthopsilosis, C. metapsilosis, C. guilliermondii, C. pelliculosa, C. tropicalis, C. glabrata, C. famata, C. krusei, C. norvegensis, C. ciferri , Trichosporon sp., Rhodotorula sp., Cryptococcus laurentii) and 29 were from T. manatus (C. albicans, C. tropicalis, C. famata, C. guilliermondii, C. krusei, Rhodotorula sp., R. mucilaginous, R. minuta, Trichosporon sp.). This was the first systematic study to investigate the importance of yeasts as components of the microbiota of sirenians, demonstrating the presence of potentially pathogenic species, which highlights the importance of maintaining adequate artificial conditions for the health of captive manatees.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author