Antimicrobial and antiviral activities of an actinomycete (Streptomyces sp.) isolated from a Brazilian tropical forest soil

A promising producer of bioactive compounds isolated from a Brazilian tropical soil was tested for its range of antimicrobial activities. Strain 606, classified as Streptomyces sp., could not be identified up to species level, suggesting a possible new taxon. The supernatant and 10 extracts and fractions, obtained by extraction and chromatographic techniques, presented antimicrobial activity using antibiograms. The methanolic fraction was highly active against pathogenic bacteria, phytopathogenic fungi and the human pathogenic yeast Candida albicans. It also possessed high antiviral activity inhibiting the propagation of an acyclovir-resistant herpes simplex virus type 1 strain on HEp-2 cells at non-cytotoxic concentration. The strong cytotoxic effect suggests an antitumour action. This revised version was published online in August 2006 with corrections to the Cover Date.     

Paracoccidioides brasiliensis Interferes on Dendritic Cells Maturation by Inhibiting PGE2 Production

Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in most Latin American countries, especially in Brazil, whose etiologic agent is the thermodimorphic fungus of the genus Paracoccidioides, comprising cryptic species of Paracoccidioides brasiliensis, S1, PS2, PS3 and Paracoccidioides lutzii. The mechanisms involved in the initial interaction of the fungus with cells of the innate immune response, as dendritic cells (DCs), deserve to be studied. Prostaglandins (PGs) are eicosanoids that play an important role in modulating functions of immune cells including DCs. Here we found that human immature DCs derived from the differentiation of monocytes cultured with GM-CSF and IL-4 release substantial concentrations of PGE₂, which, however, were significantly inhibited after challenge with P. brasiliensis. In vitro blocking of pattern recognition receptors (PRRs) by monoclonal antibodies showed the involvement of mannose receptor (MR) in PGE₂ inhibition by the fungus. In addition, phenotyping assays showed that after challenge with the fungus, DCs do not change their phenotype of immature cells to mature ones, as well as do not produce IL-12 p70 or adequate concentrations of TNF-α. Assays using exogenous PGE₂ confirmed an association between PGE₂ inhibition and failure of cells to phenotypically mature in response to P. brasiliensis. We conclude that a P. brasiliensis evasion mechanism exists associated to a dysregulation on DC maturation. These findings may provide novel information for the understanding of the complex interplay between the host and this fungus.     

Japanese barberry seed predation by Rhagoletis meigenii fruit flies harboring Wolbachia endosymbionts

The phytophagous fruit fly Rhagoletis meigenii harbors the bacterium Wolbachia pipientis and, together with Japanese barberry, form a tri-partite symbiosis. R. meigenii is a seed predator of invasive Japanese barberry plants and is dependent on this insect-plant interaction for reproductive success. The endosymbiotic bacterium W. pipientis is a reproductive parasite known to alter the sex ratios of offspring and the fitness of infected host insects. We investigated Japanese barberry fruit for the degree of infestation by R. meigenii and characterized the Wolbachia strain infecting R. meigenii. Densities of R. meigenii in four naturalized stands of Japanese barberry revealed low numbers of fruit flies with high variability in the population densities observed among individual plants. Overall, R. meigenii infested roughly 10–20 % of the Japanese barberry fruits analyzed; fruit with two seeds (vs. one seed) were the most frequently infested. Approximately, 90 % of the R. meigenii tested positive for Wolbachia infection via PCR amplification of the Wolbachia surface protein (wsp) gene. No bacterial strain diversity was observed when comparing multi-locus sequence typing (MLST) profiles within or among five R. meigenii populations in Maine, although the MLST profile obtained from R. meigenii differed from three co-occurring Rhagoletis. The Wolbachia endosymbiont of R. meigenii is a member of the Wolbachia supergroup A and the ST-13 cluster complex.     

Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis.     

Developmental changes in the intraplacental distribution of placental lactogen and alkaline phosphatase in the rat

The junctional and labyrinth regions of the rat chorioallantoic placenta during the second half of gestation showed different patterns of development with regard to DNA, protein, placental lactogen and alkaline phosphatase content. DNA and protein measurements indicated that growth of the labyrinth region was more rapid and persisted for longer during gestation than did growth in the junctional zone. At midpregnancy the junctional zone was the main source of placental lactogen whereas by late pregnancy both regions contributed considerable amounts. On Day 20 of gestation the labyrinth region contained significantly more placental lactogen than did the junctional zone. Alkaline phosphatase activity was predominant in the labyrinth zone throughout the second half of gestation. The results indicate that the chorioallantoic placenta is composed of two functionally distinct regions.