Papers by Rodrigo Holanda
Antibiotics
Failures in endodontic treatments are mostly associated with the difficulty in eradicating microb... more Failures in endodontic treatments are mostly associated with the difficulty in eradicating microbes of the root canal system, highlighting the need to develop novel effective antimicrobials. Punica granatum (pomegranate) leaf hydroalcoholic extract may be a potential alternative in canal dressing, owing to its antimicrobial properties. The objective of this study was to evaluate the antimicrobial activity of hydroalcoholic leaf extract of Punica granatum (HEPg) alone or in combination with calcium hydroxide (Ca(OH)2) against Enterococcus faecalis and Candida albicans in isolation and in mono- and polymicrobial biofilms. Microdilution tests in broth and assays for inhibition of biofilm formation were carried out to evaluate the antimicrobial properties of HEPg and HEPg + Ca(OH)2 against Enterococcus faecalis and Candida albicans. The cytotoxicity of HEPg in HaCaT cells was evaluated by MTT assay. HEPg and HEPg + Ca(OH)2 exerted significant antimicrobial activity against planktonic ce...
Medical Mycology
Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction Paracoccidioidomycosis is... more Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction Paracoccidioidomycosis is a systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis. The disease is restricted to Latin America. It is the principal systemic mycosis in Brazil, with higher incidences in the southern, southeastern and central regions. Objectives It's to report a case of paracoccioidomycosis with a bizarre presentation on the face. Case Report A 54-year-old male farmer from Açailândia, Maranhão, with a history of an extensive ulcerated lesion that started in the right wing of the nose. After 6 months of evolution, the lesion had already spread reaching the nasal and oral mucosa, evolving with acute respiratory failure, requiring tracheostomy (Fig.1). He was referred to the Cancer Hospital for a biopsy, which was referred for pathological examination, showing an intense inflammatory infiltrate consisting of lymphocytes, histiocytes, neutrophilis with giant, multinucleated ...
Research, Society and Development
A Doença do Coronavírus-2019 (COVID-19), maior pandemia registrada no século XXI, se trata de uma... more A Doença do Coronavírus-2019 (COVID-19), maior pandemia registrada no século XXI, se trata de uma infecção respiratória aguda com potencial gravidade. Dentre os sintomas decorrentes da doença, a perda sensorial, como a ageusia, representa um desafio entre pesquisadores, uma vez que os mecanismos relacionados à fisiopatologia viral contra as células neurosensitivas ainda não estão totalmente esclarecidos. Diante desse contexto, esse estudo visou revisar a literatura recente sobre a perda da sensação do paladar e a infecção por SARS-CoV-2. Para isso, foi realizado uma revisão narrativa, pesquisando artigos das principais bases de dados, como PubMed, Scielo e Google Acadêmico, e selecionando os que possuíam afinidade com a temática proposta. Através do estudo, verificou-se que a ageusia é um sintoma comum em pacientes com COVID-19, devido, principalmente, à presença significativa dos receptores celulares que medeiam a infecção viral na região oral. Os mecanismos sugeridos para explicar...
Ciência e Natura, 2020
Cryptococcosis is an invasive mycosis triggered by a complex of fungal pathogens present in vario... more Cryptococcosis is an invasive mycosis triggered by a complex of fungal pathogens present in various environmental niches. Cryptococcus neoformans, C. gattii, and emerging pathogens such as C. laurentii and C. albidus are found in aged excreta of Columba livia (pigeon), its natural disseminator. As the pigeon population has increased in São Luís, the objective of this research was to demonstrate the presence of Cryptococcus spp. in the excreta of C. livia in public environments. Twenty-three samples were collected at 14 sites, dispensed into conical tubes, homogenized with saline and chloramphenicol, and allowed to rest until processing. Twenty-four hours after collection, aliquots were distributed in a fungal culture medium and incubated. The macromorphological examination revealed levaduriform, mucoid, bright, isolated colonies compatible with Cryptococcus spp. In the micromorphological examination, 11 of the 23 samples (42.85%) showed the presence of cells with a thick, refringent...
Green Sustainable Process for Chemical and Environmental Engineering and Science, 2022
Journal of Pharmacy and Pharmacology, 2020
Abstract: Here, we evaluated the clinical aspects and environmental factors for five cases of pne... more Abstract: Here, we evaluated the clinical aspects and environmental factors for five cases of pneumocystosis in the eastern Brazilian Amazon. Pneumocystosis was associated with human immunodeficiency virus (HIV) infection, male sex, age (until 30 years), and treatment with sulfamethoxazole plus trimethoprim in 100%, 80%, 40%, and 80% cases, respectively. Drier months, higher temperatures, and wind speed were favorable variables for pneumocystosis. Overall, this fungal infection may be related to global warming, resulting in an increased occurrence of cases.
Journal of Fungi, 2021
Limosilactobacillus fermentum (ATCC 23271) was originally isolated from the human intestine and h... more Limosilactobacillus fermentum (ATCC 23271) was originally isolated from the human intestine and has displayed antimicrobial activity, primarily against Candida species. Complete genome sequencing and comparative analyses were performed to elucidate the genetic basis underlying its probiotic potential. The ATCC 23271 genome was found to contain 2,193,335 bp, with 2123 protein-coding sequences. Phylogenetic analysis revealed that the ATCC 23271 strain shares 941 gene clusters with six other probiotic strains of L. fermentum. Putative genes known to confer probiotic properties have been identified in the genome, including genes related to adhesion, tolerance to acidic pH and bile salts, tolerance to oxidative stress, and metabolism and transport of sugars and other compounds. A search for bacteriocin genes revealed a sequence 48% similar to that of enterolysin A, a protein from Enterococcus faecalis. However, in vitro assays confirmed that the strain has inhibitory activity on the grow...
Frontiers in Microbiology, 2021
Cryptococcosis, caused by yeasts of the genus Cryptococcus, is an infectious disease with a world... more Cryptococcosis, caused by yeasts of the genus Cryptococcus, is an infectious disease with a worldwide distribution. Cryptococcus neoformans and Cryptococcus gattii are the species that commonly cause this disease in humans; however, infections caused by Cryptococcus laurentii, especially in immunocompromised patients, are increasingly being reported. Owing to the increase in the resistance of fungi to antifungals, and a lack of treatment options, it is important to seek new therapeutic alternatives such as natural products. Among these are plant species such as Punica granatum, which is used in folk medicine to treat various diseases. This study aimed to evaluate the activity of the acetate fraction of P. granatum leaf extract against environmental and clinical isolates of Cryptococcus. Three environmental isolates of C. laurentii, PMN, PMA, and PJL II, isolated from soils of different municipalities in the state of Maranhão, a clinical isolate, C. gattii, from a patient with neuroc...
Medical Mycology, 2020
Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and sub... more Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone...
Mycoses, 2019
The infections caused by fungi represent a global concern and an important cause of hospital admi... more The infections caused by fungi represent a global concern and an important cause of hospital admissions in endemic areas. The influence of socio‐environmental factors in infectious diseases has been documented; however, this phenomenon remains unclear regarding mycoses.
Pathogens, 2019
Candida yeasts are generally found in the vaginal microbiota; however, disruption of the balance ... more Candida yeasts are generally found in the vaginal microbiota; however, disruption of the balance maintained by host factors and microorganisms results in vulvovaginal candidiasis (VVC). This study evaluated the antagonistic activity of vaginal Lactobacillus spp. on Candida albicans to verify whether active compounds of Lactobacillus spp. had antifungal and antivirulence activity. The antagonism assay showed that 15 out of 20 Lactobacillus strains had an inhibitory effect on C. albicans. Biosurfactants displayed surface-tension-reducing activity, with the best value obtained for Lactobacillus gasseri 1. Lactobacillus rhamnosus ATCC 9595, Lactobacillus acidophilus ATCC 4356, and Lactobacillus paracasei 11 produced biosurfactants that decreased C. albicans adhesion and disrupted biofilm formation. The best results were obtained in the pre-incubation assay for L. gasseri 1 and L. paracasei 11. Overall, Lactobacillus strains showed significant anti-Candida activity, and their biosurfacta...
MicrobiologyOpen, Apr 26, 2017
Trying to widen the discussion on the risks associated with dental waste, this study proposed to ... more Trying to widen the discussion on the risks associated with dental waste, this study proposed to investigate and genetically compare yeast isolates recovered from dental solid waste and waste workers. Three samples were collected from workers' hands, nasal mucosa, and professional clothing (days 0, 30, and 180), and two from dental waste (days 0 and 180). Slide culture, microscopy, antifungal drug susceptibility, intersimple sequence repeat analysis, and amplification and sequencing of internal transcribed spacer regions were performed. Yeast strains were recovered from all waste workers' sites, including professional clothes, and from waste. Antifungal susceptibility testing demonstrated that some yeast recovered from employees and waste exhibited nonsusceptible profiles. The dendrogram demonstrated the presence of three major clusters based on similarity matrix and UPGMA grouping method. Two branches displayed 100% similarity: three strains of Candida guilliermondii isolat...
Fungal biology, Dec 1, 2017
We assessed the diversity of cultivable fungi in the ornithogenic soil nests of bird species like... more We assessed the diversity of cultivable fungi in the ornithogenic soil nests of bird species like Phalacrocorax atriceps, Macronectes giganteus, Pygoscelis antarcticus, and Pygoscelis papua in the Antarctic islands. From 481 fungi isolated at 15 °C, only 50 displayed growth at 37 °C, and were identified as 14 species of 15 genera. Aspergillus fumigatus, Penicillium chrysogenum, and Rhodotorula mucilaginosa were the most abundant species obtained. Fifty taxa grew at 40 °C; displayed haemolytic and phospholipase activities; produced tiny spores, capsule, and melanin; showed growth at different pH; and showed resistance to amphotericin B. Interestingly, the minimum inhibitory concentration of amphotericin B increased by 5-10 fold for some A. fumigatus isolates after phagocytosis by amoeba. Our results show relations among fungal community compositions present in Antarctic ornithogenic soil and their pathogenic risk to humans in vitro. As the Antarctica Peninsula is a major region of th...
PLoS neglected tropical diseases, Jan 22, 2017
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the the... more Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous pri...
Scientific reports, Jul 5, 2017
Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds... more Cryptococcus spp., the causative agents of cryptococcosis, are responsible for deaths of hundreds of thousands of people every year worldwide. The drawbacks of available therapeutic options are aggravated by the increased resistance of yeast to the drugs, resulting in inefficient therapy. Also, the antifungal 5FC is not available in many countries. Therefore, a combination of antifungal drugs may be an interesting option, but in vitro and theoretical data point to the possible antagonism between the main antifungals used to treat cryptococcosis, i.e., fluconazole (FLC), and amphotericin B (AMB). Therefore, in vivo studies are necessary to test the above hypothesis. In this study, the efficacy of FLC and AMB at controlling C. gattii infection was evaluated in a murine model of cryptococcosis caused by C. gattii. The infected mice were treated with FLC + AMB combinations and showed a significant improvement in survival as well as reduced morbidity, reduced lung fungal burden, and the ...
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Jan 25, 2016
The emergence of fluconazole-resistant Cryptococcus gattii is a global concern, since this azole ... more The emergence of fluconazole-resistant Cryptococcus gattii is a global concern, since this azole is the main antifungal used worldwide to treat patients with cryptococcosis. Although pharmacokinetic (PK) and pharmacodynamic (PD) indices are useful predictive factors for therapeutic outcomes, there is a scarcity of data regarding PK/PD analysis of antifungals in cryptococcosis caused by resistant strains. In this study, PK/PD parameters were determined in a murine model of cryptococcosis caused by resistant C. gattii. We developed and validated a suitable liquid chromatography-electrospray ionization tandem mass spectrometry method for PK studies of fluconazole in the serum, lungs, and brain of uninfected mice. Mice were infected with susceptible or resistant C. gattii spp., and the effects of different doses of fluconazole on the pulmonary and central nervous system fungal burden were determined. The peak levels in the serum, lungs, and brain were achieved within 0.5 h. The AUC/MIC ...
BMC Infectious Diseases, 2016
Antimicrobial Agents and Chemotherapy, 2015
Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individual... more Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11 C. gattii strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of origina...
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Papers by Rodrigo Holanda