Because of the importance of the different yeast ligands and host receptors on the intracellular fate of phagocytosed yeast, the repertoire of surface

find more molecules that engage host phagocytes might contribute to phenotypic differences between Histoplasma strains. Future experiments that examine blockage of the candidate adhesins in G186A yeast will be needed to resolve this question. Catalases are hydrogen peroxide metabolizing enzymes often utilized by pathogens to ameliorate the effects of anti-microbial reactive oxygen. The immunoreactive M-antigen found in Histoplasma culture filtrates corresponds to the CatB catalase protein (Hamilton et al., 1990; Zancope-Oliveira et al., 1999). Although originally prepared from mycelial-phase cultures, CatB is also an exoantigen of both G186A and G217B yeast

cells. Patient antibodies to CatB confirm that the yeast produce this protein during infection. However, CatB regulation differs between strains. In G186A, the CATB gene shows approximately 100-fold higher expression in yeast than in mycelia, and this protein is expressed by G186A yeast in vitro, in macrophages, and in the mouse lung (Holbrook et al., 2011). In contrast, there is equivalent transcription of CATB in both yeast and mycelial phases of G217B (Johnson et al., 2002). In addition, differences have been NVP-BGJ398 price found in the extracellular localization of CatB between the strains. In G186A, cell wall-associated catalase is a minor contributor to the total extracellular peroxidase activity with the majority present in the soluble extracellular fraction (Holbrook et al., 2011). For G217B, CatB is found primarily

associated with the yeast cell wall, being released only after 7 days of culture Aspartate (Guimaraes et al., 2008). The functional consequences of the differing regulation and localization of CatB remain to be determined but these findings continue to highlight the variability between strains that may contribute to differences in virulence phenotypes. Additional variability in cellular composition and secreted factors correlate with the deeply branching Histoplasma phylogenetic groups. In a survey of cellular lipids, distinct fatty acid compositions of yeast cells were found to exist among the Histoplasma strains (Zarnowski et al., 2007b). The Histoplasma H-antigen (Hag1; β-glucosidase) is produced by all strains, but G217B yeast release over ten times as much β-glucosidase activity (Fisher et al., 1999). In addition, the H-antigen produced by each strain varies in size with Panamanian strains producing a smaller protein than NAm1 and NAm2 strains. Both NAm2 and Latin American strains express surface-localized Histone-2B and melanin on yeast cells (Nosanchuk et al., 2002, 2003).