Biochemistry and biology of antigen presentation by macrophages

The presentation of antigen by macrophages has been studied. We have shown that globular proteins must be processed in endocytic vesicles of low pH prior to presentation. Some of the structural requirements of one such processed peptide have been determined, as has the affinity for Ia of that peptide. Finally, we have shown that a membrane-associated form of interleukin-1 is also required for presentation of processed antigen to T cells.     

Biochemistry and cell signaling taught by bacterial effectors

Bacterial virulence often relies on secreted effectors that modulate eukaryotic signal transduction. Recent studies provide a collection of examples in which bacterial effectors carry out unprecedented posttranslational modifications of key signaling molecules or organize a new signaling network. OspF and YopJ families of effectors use novel modification activities to block kinase phosphoactivation. Targeting of the ubiquitin system by IpaH and Cif/CHBP families provides insights into host ubiquitin signaling. Manipulation of small GTPases by VopS/IbpA and SidM suggests previously underappreciated regulation of signaling. Several other effectors, including SifA and EspG, organize newly discovered signaling networks in membrane trafficking. Studies of these effectors can generate new knowledge in enzyme catalysis and provide new angles for furthering our understanding of biochemical regulation of important signaling pathways.     

Biochemistry of insect epicuticle degradation by entomopathogenic fungi

The biochemical interaction between fungal pathogens and their insect host epicuticle was studied by examining fungal hydrocarbon degrading ability. As a contact insecticide, entomopathogenic fungi invade their host through the cuticle, covered by an outermost lipid layer mainly composed of highly stable, very long chain structures. Strains of Beauveria bassiana and Metarhizium anisopliae (Deuteromycotina: Hyphomycetes), pathogenic both to the blood-sucking bug Triatoma infestans (Hemiptera: Reduviidae) and the bean-weevil Acanthoscelides obtectus (Coleoptera, Bruchidae), were grown on different carbon sources. Alkane-grown cells showed a lipid pattern different from that of glucose-grown cells, evidenced by a major switch in the triacylglycerol and sterol components. Radiolabelled hydrocarbons were used to investigate the catabolic pathway and the by-product incorporation into fungal cellular components. The first oxidation round is presumably carried out by a cytochrome P450 enzyme system, the metabolites will traverse the peroxisomal membrane, and after successive transformations will eventually provide the appropriate fatty acyl CoA for complete degradation in the peroxisomes, the site of beta-oxidation in fungi. In this review, we will show the relationship between fungal ability to catabolize very long chain hydrocarbons and virulence parameters.