Antifúngicos naturais e sintéticos: estudo dos mecanismos de ação em sistema de infecção in vitro empregando cepas de Cryptococcus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efetividade da terapia fotodinâmica na inativação de Candida spp

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The role of native vegetation on infection rates of Calacarus heveae (Acari: Eriophyidae) by Hirsutella thompsonii (Ascomycota: Ophiocordycipitaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Leaf-cutting ants: an unexpected microenvironment holding human opportunistic black fungi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adesão de Paracoccidioides brasiliensis e outros fungos anemófilos a teias de aranhas: implicações para a identificação de nichos microbianos no ambiente

The dimorphic pathogenic fungus, Paracoccidioides brasiliensis (Pb), is the etiological agent of paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. While the yeast phase can be isolated from patients affected by paracoccidioidomycosis, dogs and naturally infected armadillos; several elements related to the ecology of the saprophytic phase of the pathogen, which is responsible for the production of infective propagules, are poorly understood, hampering the adoption of preventive measures. The demonstration of the high incidence of Pb infection in the 9- banded armadillo, Dasypus novemcinctus, has opened new perspectives for the identification of the pathogen’s habitat. At the opening of the armadillos’ burrows, spider webs are commonly found. The objective of this study was to evaluate the presence of Pb in spider webs samples related to the habitat of armadillos. Spider web samples were collected at Lageado Farm, Botucatu/SP and prepared for microscopic, molecular and mycological analyses. Microscopic analysis showed that different fungi were closely attached to spider web samples. Nested-PCR reaction showed positive amplification for Pb in 4 samples, with identity confirmed by amplicon sequencing. Fungal colonies also included members of Aspergillus, Blastobotrys, Penicillium, Candida, and Sporothrix genera, which are related to opportunistic disease and primary infections of great medical importance. In vitro adhesion tests of mycelia and yeast form of Pb to the spider webs were also performed, in order to analyze the possible physical attraction between fungal cells and the spider web protein network. The results showed a clear adherence of fungal particles to spider webs. In the current literature, there are no studies reporting adhesive properties of microorganisms to spider webs... (Complete abstract click electronic access below)

Experimental Autoimmune Encephalomyelitis Development Is Aggravated by Candida albicans Infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The receptor-like kinase SlSOBIR1 is differentially modulated by virus infection but its overexpression in tobacco has no significant impact on virus accumulation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A mini review of Candida species in hospital infection: epidemiology, virulence factor and drugs resistance and prophylaxis

The introduction of more efficient diagnostic methods, new techniques in surgery and transplantation, antibiotics and chemotherapeutics more potent and novel materials for prostheses, catheters and probes significantly increased the life expectancy and quality of life of critically ill patients, on the other hand, hospital-acquired infections emerged as important iatrogenic complications. Invasive infections are a growing problem in public health hospitals in Brazil and worldwide. Among the various etiological agents found in the hospital environment, the genus Candida has been the third most frequently isolated pathogen. In general, invasive fungal infections are associated with high morbidity and mortality, difficulties in diagnosis, antimicrobial resistance, length of hospital stay and increased hospital costs. This mini review of the literature describes about epidemiology of hospital infection of Candida species, as well as its virulence factors and drugs resistance

Estudo de genes de Candida albicans com função desconhecida quanto à formação de biofilme, características biológicas e interação patógeno- hospedeiro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

SIGNIFICANCE AND CONTROL OF FUNGAL DISEASES RELATED TO BIRD ROOSTS

Certain fungi have been found frequently as saprophytes in areas containing large amounts of bird excreta. These fungi have the ability to survive, multiply, and cause disease once they have entered a host. Two of these are Crypto-coccus neoformans and Histoplasma capsulatum. Both may easily become airborne and be disseminated throughout an area by the prevailing winds. C. neo-formans is commonly isolated from the excreta of pigeon habitats, and in turn has been associated with clinical cases of cryptococcosis, while blackbird roosts, harboring H. capsulatum, have been responsible for several outbreaks of histoplasmosis. When either of these fungi have become established in nature, the sites may become foci for infection and epidemics may occur if the sites are disturbed. This has led to investigation of these organisms with respect to: 1) the frequency of isolation of H. capsulatum from the soil beneath blackbird roosts in a histoplasmosis endemic area; 2) the infectivity of undisturbed roosts positive for H. capsulatum; and 3) the effectiveness of chemical decontamination of areas containing C. neoformans or H. capsulatum.

Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections

Aims: To quantify and compare the expression of Langerhans cells (LCs) in the tongue mucosa of AIDS patients with different opportunistic infections, and from acquired immune deficiency syndrome (AIDS) and non-AIDS patients with normal tongues, using autopsy material. Methods and results: Human leucocyte antigen D-related (HLA-DR), CD1a and CD83 antibodies were used to identify and quantify LCs by immunohistochemistry in tongue tissue of 40 AIDS patients (10 with lingual candidiasis, 10 with lingual herpes, 10 with oral hairy leukoplakia and 10 with no lesions) and 23 tongues from human immunodeficiency virus (HIV)negative control patients. Quantification was performed by means of conventional morphometry in four different regions (anterior, middle, posterior and lateral) of the tongue. The results were expressed as positive cells per area of epithelium. The AIDS patients presented a lower density of CD1a(+) cells (P < 0.001), HLA-DR (P < 0.003) and CD83 (P < 0.001) in all regions of the tongue compared to the non-AIDS control group. However, no differences in any of the markers were found when AIDS patients with different opportunistic infections were compared with AIDS patients without tongue infection. Conclusions: Advanced stage AIDS patients showed a depletion of LCs in the tongue mucosa. HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients. Lupus (2012) 21, 1011-1016.

Comparative Genome Analysis of Trichophyton rubrum and Related Dermatophytes Reveals Candidate Genes Involved in Infection

The major cause of athlete's foot is Trichophyton rubrum, a dermatophyte or fungal pathogen of human skin. To facilitate molecular analyses of the dermatophytes, we sequenced T. rubrum and four related species, Trichophyton tonsurans, Trichophyton equinum, Microsporum canis, and Microsporum gypseum. These species differ in host range, mating, and disease progression. The dermatophyte genomes are highly colinear yet contain gene family expansions not found in other human-associated fungi. Dermatophyte genomes are enriched for gene families containing the LysM domain, which binds chitin and potentially related carbohydrates. These LysM domains differ in sequence from those in other species in regions of the peptide that could affect substrate binding. The dermatophytes also encode novel sets of fungus-specific kinases with unknown specificity, including nonfunctional pseudokinases, which may inhibit phosphorylation by competing for kinase sites within substrates, acting as allosteric effectors, or acting as scaffolds for signaling. The dermatophytes are also enriched for a large number of enzymes that synthesize secondary metabolites, including dermatophyte-specific genes that could synthesize novel compounds. Finally, dermatophytes are enriched in several classes of proteases that are necessary for fungal growth and nutrient acquisition on keratinized tissues. Despite differences in mating ability, genes involved in mating and meiosis are conserved across species, suggesting the possibility of cryptic mating in species where it has not been previously detected. These genome analyses identify gene families that are important to our understanding of how dermatophytes cause chronic infections, how they interact with epithelial cells, and how they respond to the host immune response. IMPORTANCE Athlete's foot, jock itch, ringworm, and nail infections are common fungal infections, all caused by fungi known as dermatophytes (fungi that infect skin). This report presents the genome sequences of Trichophyton rubrum, the most frequent cause of athlete's foot, as well as four other common dermatophytes. Dermatophyte genomes are enriched for four gene classes that may contribute to the ability of these fungi to cause disease. These include (i) proteases secreted to degrade skin; (ii) kinases, including pseudokinases, that are involved in signaling necessary for adapting to skin; (iii) secondary metabolites, compounds that act as toxins or signals in the interactions between fungus and host; and (iv) a class of proteins (LysM) that appear to bind and mask cell wall components and carbohydrates, thus avoiding the host's immune response to the fungi. These genome sequences provide a strong foundation for future work in understanding how dermatophytes cause disease.

Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection

Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis. Therefore, we sought to characterize, for the first time, the transcriptional profile of murine bone marrow-derived dendritic cells (DCs) at an early stage following their initial interaction with P. brasiliensis. DCs connect innate and adaptive immunity by recognizing invading pathogens and determining the type of effector T-cell that mediates an immune response. Gene expression profiles were analyzed using microarray and validated using real-time RT-PCR and protein secretion studies. A total of 299 genes were differentially expressed, many of which are involved in immunity, signal transduction, transcription and apoptosis. Genes encoding the cytokines IL-12 and TNF-alpha, along with the chemokines CCL22, CCL27 and CXCL10, were up-regulated, suggesting that P. brasiliensis induces a potent proinflammatory response in DCs. In contrast, pattern recognition receptor (PRR)-encoding genes, particularly those related to Toll-like receptors, were down-regulated or unchanged. This result prompted us to evaluate the expression profiles of dectin-1 and mannose receptor, two other important fungal PRRs that were not included in the microarray target cDNA sequences. Unlike the mannose receptor, the dectin-1 receptor gene was significantly induced, suggesting that this beta-glucan receptor participates in the recognition of P. brasiliensis. We also used a receptor inhibition assay to evaluate the roles of these receptors in coordinating the expression of several immune-related genes in DCs upon fungal exposure. Altogether, our results provide an initial characterization of early host responses to P. brasiliensis and a basis for better understanding the infectious process of this important neglected pathogen.

Opportunistic and Other Infections in HIV-Infected Children in Latin America Compared to a Similar Cohort in the United States

Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U. S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.