PRP8 intein in Ajellomycetaceae family pathogens: Sequence analysis, splicing evaluation and homing endonuclease activity

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

Defense reactions of Dermatobia hominis (Diptera : Cuterebridae) larval hemocytes

The defense reactions against biological (Histoplasma capsulatum and Escherichia coli) and non-biological materials (China ink and nylon thread) were tested in vivo in third instar larvae of Dermatobia hominis. The cellular defense performed by larval hemocytes was observed under electron microscopy. China ink particles were phagocytosed by granular cells 5 h after injection. E. coli cells were internalized by granular cells as early as 5 min after injection and totally cleared 180 min post-injection, when many hemocytes appeared disintegrated and others in process of recovering. H. capsulatum yeasts provoked, 24 h after being injected, the beginning of nodule formation. Nylon thread was encapsulated 24 h after the introduction into the hemocoel. Our results suggest that granular cells were the phagocytic cells and also the responsible for the triggering of nodule and capsule formation. In the presence of yeasts cells and nylon thread, they released their granules that chemotactically attracted the plasmatocytes that on their turn, flattened to surround and isolate the foreign material.

Virulence Factors IN Fungi of Systemic Mycoses

Fatores de virulência em fungos de micoses sistêmicaFungos patogênicos causadores de micoses sistêmicas possuem vários fatores que permitem seu crescimento nas condições adversas oferecidas pelo hospedeiro, propiciando o estabelecimento da relação parasitária e contribuindo no processo de doença. Esses fatores são conhecidos como fatores de virulência auxiliando no desenvolvimento da infecção e interferindo com a patogênese das micoses. O presente trabalho avalia os fatores de virulência em fungos patogênicos como Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum e Paracoccidioides brasiliensis, em relação à termotolerância, dimorfismo, componentes da parede celular ou cápsula, bem como a produção de enzimas. Os fatores de virulência auxiliam na aderência, colonização, disseminação e habilidade do fungo para resistir a ambientes hostis e escapar dos mecanismos da resposta imune do hospedeiro.Tanto os fatores de virulência apresentados por diferentes fungos, como os mecanismos de defesa oferecidos pelo hospedeiro requerem ação e interação de processos complexos, cujo conhecimento permitirá a melhor compreensão da patogenia das micoses sistêmicas.

Immunosuppression in paracoccidioidomycosis: T cell hyporesponsiveness to two Paracoccidioides brasiliensis glycoproteins that elicit strong humoral immune response

To assess human cellular immune response to paracoccidioidomycosis (PCM), lymphocyte proliferative responses to purified antigens from Paracoccidioides brasiliensis were determined in healthy persons previously infected by the fungus (positive donors), in healthy noninfected persons (controls), and in PCM patients. Affinity-purified gp70 and gp43, the two major antigens in humoral immune responses, were used, Both induced lymphocyte proliferation (gp43 species-specific) in positive donors but not in controls; healthy persons previously infected by Histoplasma capsulatum reacted to gp70 and not to gp43, A similar cross-reactivity in antibody response to gp70 was previously reported; however, antibody response to gp43 has been considered specific, Lymphocytes from PCM patients, who, unlike positive donors, have high levels of anti-gp43 and anti-gp70 antibodies, proliferated poorly with gp70 and gp43 but better with other stimuli, This dichotomy between humoral and cellular antigen-specific responses suggests a Th2 immune response in PCM, which may be related to failure to control the infection.

EARLY ACTIVATION OF SPLENIC MACROPHAGES BY TUMOR-NECROSIS-FACTOR-ALPHA IS IMPORTANT IN DETERMINING THE OUTCOME OF EXPERIMENTAL HISTOPLASMOSIS IN MICE

Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection.

Phylogenetic and evolutionary aspects of Paracoccidioides brasiliensis reveal a long coexistence with animal hosts that explain several biological features of the pathogen

The habitat of the mycelial saprobic form of Paracoccidio ides brasiliensis, which produces the infectious propagula, has not been determined and has proven difficult for mycologists to describe. The fungus has been rarely isolated from the environment, the disease has a prolonged latency period and no outbreaks have been reported. These facts have precluded the adoption of preventive measures to avoid infection. The confirmation of natural infections in nine-banded armadillos (Dasypus novemcinctus) with P. brasiliensis, in high frequency and wide geographic distribution, has opened new avenues for the study and understanding of its ecology. Armadillos belong to the order Xenarthra, which has existed in South America ever since the Paleocene Era (65 million years ago), when the South American subcontinent was still a detached land, before the consolidation of what is now known as the American continent. on the other hand, strong molecular evidence suggests that P. brasiliensis and other dimorphic pathogenic fungi - such as Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum - belong to the family Onygenaceae sensu Into (order Onygenales, Ascomycota), which appeared around 150 million years ago.P. brasiliensis ecology and relation to its human host are probably linked to the fungal evolutionary past, especially its long coexistence with and adaptation to animal hosts other than Homo sapiens, of earlier origin. Instead of being a blind alley, the meaning of parasitism for dimorphic pathogenic fungi should be considered as an open two-way avenue, in which the fungus may return to the environment, therefore contributing to preserve its teleomorphic (sexual) and anamorphic (asexual) forms in a defined and protected natural habitat. (c) 2006 Elsevier B.V. All rights reserved.

5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

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

Histoplasmose do esôfago: Relato de caso

The authors report a case of a patient with complaint of progressive disphagia. Stenoses of lower third of esophagus was revealed by radiological and endoscopic examinations. Fungi were showed in biopsy of lesion, with demonstration of Histoplasm capsulate by tissue culture. Endoscopic dilatation was performed because especific medical treatment failed but esophageal rupture was observed. Partial esophagectomy was performed with symptoms remission.

IgG, IgM and IgA antibody response for the diagnosis and follow-up of paracoccidioidomycosis: Comparison of counterimmunoelectrophoresis and complement fixation

IgG, IgM and IgA antibodies to GP43 (glycoprotein fraction of Paracoccidioides brasiliensis) were measured by ELISA in 63 samples from 23 patients with paracoccidioidomycosis before and twice after chemotherapy was started. Antibodies against P. brasiliensis were detected by indirect immunofluorescence (IF) (IgG, IgM and IgA isotypes), counterimmunoelectrophoresis (CIE) and complement fixation. Two control groups composed of 19 healthy individuals and 12 patients with other diseases (six with histoplasmosis, three with tuberculosis and three with other mycoses). The highest efficiency percentages were found with IgG and IgA- ELISA (100%), IgG-IF (96.2%), CIE (94.4%) and the lowest with CF (75.9%). Highest positive and negative predictive values (100%) were observed for IgG and IgA ELISA. IgG and IgM-ELISA antibodies are more often found in patients with acute than chronic disease (P = 0.01). Four to six months after treatment follow-up showed decreased levels of IgG and IgM-ELISA for acute cases and decreased titres of CIE for chronic cases in relation to pretreatment levels. This study suggests that IgG-ELISA anti-GP43 represents a good marker to monitor clinical response to therapy.

Estudo da mcrobiota fúngica gastrintestinal de morcegos (Mammalia, Chiroptera) da região noroeste do estado de São Paulo: Potencial zoonótico

Bats are hosts of a rich diversity of microorganisms. Many studies indicate a close link between bats and fungi with pathogenic potential, especially for living in environments such as caves, caverns and hollow trees, favorable to the maintenance and spread of fungi. The objective was to study the gastrointestinal mycoflora of bats. Of the 98 samples belonging to 11 species of bats coming from 15 studied cities, 20% of the species were Carollia perspicillata, 19% Artibeus lituratus, 17% Molossus rufus, 13% Glossophaga soricina, 9% Nyctinomops macrotis, 8% Molossus molossus, 7% Desmodus rotundus, 2% Lasiurus ega and 1% Eptesicus furinalis, Myotis nigricans and Tadarida brasiliensis. The genus Aspergillus sp. was isolated from 29% of the samples, followed by 6% Microsporum sp. and Penicillium sp. 4% Trichophyton sp. and zygomycetes and 2% Fusarium sp. Of yeast species, 14% were from Rhodotorula sp., 10% Candida sp. and 2% Cryptococcus sp., 22% of isolates remained unidentified. All 82 cultures of organs were negative for Histoplasma capsulatum. There was a statistically significant association between the results of microbiological culture and bat species (p < 0.05). We conclude that the bats can act as disperser agents of fungi with pathogenic potential, although other studies should be performed to establish strategies to identify the main factors correlated with the growth and spread of microorganisms in nature and implication of bats in the epidemiological cycle.

Highlights in pathogenic fungal biofilms

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

The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis

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

Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi

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

Impairment of neutrophil migration to remote inflammatory site during lung histoplasmosis

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

Primary cutaneous histoplasmosis developed in the penis of an immunocompetent patient

A 70-year-old male presenting a 3-month history of genital painless erythematous nodules in the balanopreputial sulcus was referred to our service. Histopathological exam presented a chronic dermatitis with epithelioid granulomas and Grocott staining revealed numerous fungal structures with a suggestive morphology of Histoplasma sp. Cultures evidenced Histoplasma capsulatum var. capsulatum. Treatment with oral itraconazole led to complete remission of lesions.