Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.

Experimental evidences that P21 protein controls Trypanosoma cruzi replication and modulates the pathogenesis of infection

P21 is a protein secreted by Trypanosoma cruzi (T. cruzi). Previous studies have shown a spectrum of biological activities performed by P21 such as induction of phagocytosis, leukocyte chemotaxis and inhibition of angiogenesis. However, the activity of P21 in T. cruzi infection remains unknown. Here, we reported the role of P21 in mice harboring late T. cruzi infection. Treatment with recombinant P21 protein (rP21) reduced parasite load and angiogenesis, and induced fibrosis in the cardiac tissue of infected mice. In addition, rP21 reduced the growth of epimastigotes, inhibited intracellular replication of amastigotes and modulated the parasite cell cycle. Our data suggest that P21 controls parasite replication in the host, supporting the survival of both parasite and host.

Bioassay-guided fractionation and antimicrobial and cytotoxic activities of Cassia bakeriana extracts

ABSTRACT The antimicrobial potential of extracts of bark and leaves of Cassia bakeriana Craib, Fabaceae, against aerobic and anaerobic oral bacteria was evaluated by the microdilution broth method. For crude ethanol extracts and organic fractions tested, the bark dichloromethane phase showed a significant antibacterial effect, with MIC values ranging from 12.5 to 100 µg/ml for most of the microorganisms tested. Thus, a bioassay-guided fractionation of this fraction was performed. This fractionation led to isolation of the 1,8-dihydroxy-anthraquinone-3-carboxylic acid, also known as cassic acid or rhein. It is the first time that this bioactive anthraquinone has been isolated from this plant. Rhein exhibited good selectivity and high activity against anaerobic microorganisms, with MIC values ranging between 3.12 µg/ml (11.0 µM) and 25 µg/ml (88.0 µM). These results were considered very promising since the most active samples and rhein showed greater selectivity against oral microorganisms than toxicity to Vero cells.

Intestinal parasitic infections in HIV/AIDS patients: experience at a teaching hospital in central Brazil.

In order to verify the occurrence of intestinal parasitic infections in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients, 100 HIV/AIDS patients (Group 1) and 85 clinically healthy individuals (Group 2) were submitted to coproparasitological examination. Intestinal parasites were detected in 27% of patients from Group 1 and in 17.6% from Group 2. In Group 1 the most frequent parasites were Strongyloides stercoralis (12%), with 2 cases of hyperinfection; Isospora belli, 7%; Cryptosporidium sp., 4%; with 1 asymptomatic case and hookworm, 4%. Of the infected patients from Group 1 who reported to be chronic alcoholics, 64.3% had strongyloidiasis. Only 6 of the 27 infected patients from Group 1 were on highly antiretroviral therapy (HAART). In Group 2 the most frequent parasites were S. stercoralis, 7.1%; hookworm, 7.1% and Giardia lamblia, 3.5%. In conclusion, diagnosing intestinal parasites in HIV/AIDS patients is necessary especially in those who report to be chronic alcoholics or are not on antiretroviral treatment.

Mammalian cell invasion and intracellular trafficking by Trypanosoma cruzi infective forms.

Trypanosoma cruzi, the etiological agent of Chagas disease, occurs as different strains or isolates that may be grouped in two major phylogenetic lineages: T. cruzi I, associated with the sylvatic cycle and T. cruzi II, linked to the human disease. In the mammalian host the parasite has to invade cells and many studies implicated the flagellated trypomastigotes in this process. Several parasite surface components and some of host cell receptors with which they interact have been identified. Our work focused on how amastigotes, usually found growing in the cytoplasm, can invade mammalian cells with infectivities comparable to that of trypomastigotes. We found differences in cellular responses induced by amastigotes and trypomastigotes regarding cytoskeletal components and actin-rich projections. Extracellularly generated amastigotes of T. cruzi I strains may display greater infectivity than metacyclic trypomastigotes towards cultured cell lines as well as target cells that have modified expression of different classes of cellular components. Cultured host cells harboring the bacterium Coxiella burnetii allowed us to gain new insights into the trafficking properties of the different infective forms of T. cruzi, disclosing unexpected requirements for the parasite to transit between the parasitophorous vacuole to its final destination in the host cell cytoplasm.

Mammalian cell invasion and intracellular trafficking by Trypanosoma cruzi infective forms

O agente etiológico da doença de Chagas, Trypanosoma cruzi, ocorre como cepas ou isolados que podem ser agrupados em duas grandes linhagens filogenéticas: T. cruzi I associada ao ciclo silvestre e T. cruzi II ligada à doença humana. No hospedeiro mamífero o parasita tem que invadir células, e vários estudos relacionam as formas flageladas tripomastigotas neste processo. Diferentes componentes de superfície dos parasitas e alguns dos respectivos receptores foram identificados. Em nosso trabalho temos procurado compreender como amastigotas, que normalmente são encontrados crescendo no citoplasma, podem invadir células de mamíferos com infectividade comparável às dos tripomastigotas. Encontramos diferenças nas respostas celulares induzidas por amastigotas e tripomastigotas em relação a componentes de citoesqueleto e projeções de membrana ricas em actina. Amastigotas de cepas de T. cruzi I gerados extracelularmente, podem apresentar infectividade maior que tripomastigotas metacíclicos para linhagens celulares e células com expressão alterada em diferentes classes de componentes celulares. Células albergando a bactéria Coxiella burnetii tem nos permitido obter novos enfoques sobre as propriedades de tráfego intracelular das diferentes formas infectivas do T. cruzi, revelando requerimentos inesperados para o parasita transitar entre seu vacúolo parasitóforo até seu destino final no citoplasma da célula hospedeira.