Effects of fluorinated inositols on the phosphoinositide metabolism and the proliferation of Trypanosoma cruzi.

Inositol has been cited as being essential for the growth of micro-organisms and animals. Its action rests mostly in the formation of a set of inositol-containing lipids, including phosphatidylinositol and its phosphorylated derivatives. To evaluate the functional responses coupled to the phosphoinositide metabolism in Trypanosoma cruzi we used myo-inositol and its six fluorinated analogues. Their uptake into epimastigotes was characterised using tritium-labeled myo-inositol and monodeoxyfluoro-myo-inositols. The analogues were tested for their ability to inhibit [3H]-myo-inositol incorporation into phosphoinositides and the proliferation of epimastigotes and amastigotes. The results showed differences between T. cruzi and mammalian systems in the responses to the fluorinated analogues. We found that the 3-, 5- and 6-fluoro analogues did not enter the cells but had an inhibitory effect on the incorporation of the radioactive inositol into lipids and on the amastigotes' and epimastigotes' replication. The most effective inhibitor, 1-D-6-deoxy-6-myo-inositol, had no effect on mammalian cell division.

Phospholipases C and the pathogenesis of Listeria.

Listeria monocytogenes is a model intracellular pathogen which escapes from a host cell vacuole, grows intracytoplasmically, and spreads cell to cell without an extracellular phase. A number of genes necessary for pathogenicity have been discovered, two of which encode phospholipases C, a PI-PLC and a broad-range PLC. Single and double mutants were constructed with in-frame deletions in one or both PLCs. Characterization of the strains indicated that the two PLCs may have overlapping function as the double mutant was 500-fold less virulent while the single mutants had a negligible effect on virulence. The role of the PLCs appears to be multifactorial as PI-PLC has a role in escaping from the initial host vacuole and the broad-range PLC appears to have a role in cell to cell spreading.

Phospholipases C and the pathogenesis of Listeria

Listeria monocytogenes is a model intracellular pathogen which escapes from a host cell vacuole, grows intracytoplasmically, and spreads cell to cell without an extracellular phase. A number of genes necessary for pathogenicity have been discovered, two of which encode phospholipases C, a PI-PLC and a broad-range PLC. Single and double mutants were constructed with in-frame deletions in one or both PLCs. Characterization of the strains indicated that the two PLCs may have overlapping functions as the double mutant was 500-fold less virulent while the single mutants had a negligible effect on virulence. The role of the PLCs appears to be multifactorial as PI-PLC has a role in escaping from the initial host vacuole and the broad-range PLC appears to have a role in cell to cell spreading

Isolation of a Hantaan-related virus from Brazilian rats and serologic evidence of its widespread distribution in South America.

A serosurvey of domestic rats was conducted in several South American cities between September 1982 and March 1983 for evidence of hantavirus infection. Antibody-positive rats were found in Belem, São Paulo and Recife-Olinda, Brazil and in Buenos Aires, Argentina, with the highest antibody prevalence rate detected in Belem (30 positive of 54 tested, 56%). A virus isolated from tissues of a Rattus norvegicus captured in Belem, was shown to be antigenically similar to Girard Point viruses isolated from domestic rats captured in the United States and clearly distinct from prototype Hantaan virus, causative agent of Korean hemorrhagic fever in Asia. This represents the first isolation of a virus of the genus Hantavirus from South America and supports previous observations that indicate a widespread distribution of urban rat-associated hantaviruses. The abundance of domestic rats and their regionally high antibody rates suggest that risk of human hantavirus infection in some locations of South America may be significant.