[en] Scedosporium apiospermum (Pseudallescheria boydii) is an emerging opportunistic filamentous fungus that causes serious infections in both immunocompetent and immunocompromised patients. To gain insight into the immunopathogenesis of infections due to S. apiospermum, the antifungal activities of human polymorphonuclear leukocytes (PMNs), mononuclear leukocytes (MNCs), and monocyte-derived macrophages (MDMs) against two clinical isolates of S. apiospermum were evaluated. Isolate SA54A was amphotericin B resistant and was the cause of a fatal disseminated infection. Isolate SA1216 (cultured from a successfully treated localized subcutaneous infection) was susceptible to amphotericin B. MDMs exhibited similar phagocytic activities against conidia of both isolates. However, PMNs and MNCs responded differently to the hyphae of these two isolates. Serum opsonization of hyphae resulted in a higher level of superoxide anion (O(2)(-)) release by PMNs in response to SA54A (amphotericin B resistant) than that seen in response to SA1216 (amphotericin B susceptible; P < 0.001). Despite this increased O(2)(-) production, PMNs and MNCs induced less hyphal damage to SA54A than to SA1216 (P < 0.001). To investigate the potential mechanisms responsible for these differences, hyphal damage was evaluated in the presence of antifungal oxidative metabolites as well as in the presence of a series of inhibitors and scavengers of antifungal PMN function. Mannose, catalase, superoxide dismutase, dimethyl sulfoxide, and heparin had no effect on PMN-induced hyphal damage to either of the two isolates. However, azide, which inhibits PMN myeloperoxidase activity, significantly reduced hyphal damage to SA1216 (P < 0.01) but not to SA54A. Hyphae of SA1216 were slightly more susceptible to oxidative pathway products, particularly HOCl, than those of SA54A. Thus, S. apiospermum is susceptible to antifungal phagocytic function to various degrees. The selective inhibitory pattern of azide with respect to hyphal damage and the parallel susceptibility to HOCl suggests an important difference in susceptibilities to myeloperoxidase products that may be related to the various levels of pathogenicity and amphotericin B resistance of S. apiospermum.
Babior, B. M. 2000. Phagocytes and oxidative stress. Am. J. Med. 109:33-44.
Bdeir, K., W. Cane, G. Canziani, I. Chaiken, J. Weisel, M. L. Koschinsky, R. M. Lawn, P. G. Bannerman, B. S. Sachais, A. Kuo, M. A. Hancock, J. Tomaszewski, P. N. Raghunath, T. Ganz, A. A. Higazi, and D. B. Cines. 1999. Defensin promotes the binding of lipoprotein(a) to vascular matrix. Blood 94:2007-2019.
Brajtburg, J., W. G. Powderly, G. S. Kobayashi, and G. Medoff. 1990. Amphotericin B: current understanding of mechanisms of action. Antimicrob. Agents Chemother. 34:183-188.
Carrillo, A. J., and J. Guarro. 2001. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob. Agents Chemother. 45:2151-2153.
Cuenca-Estrella, M., B. Ruiz-Diez, J. V. Martinez-Suarez, A. Monzon, and J. L. Rodriguez-Tudela. 1999. Comparative in-vitro activity of voriconazole (UK-109, 496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. J. Antimicrob. Chemother. 43:149-151.
De Lucca, A. J., and T. J. Walsh. 1999. Antifungal peptides: novel therapeutic compounds against emerging pathogens. Antimicrob. Agents Chemother. 43:1-11.
Diamond, R. D., and R. A. Clark. 1982. Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. Infect. Immun. 38:487-495.
Diamond, R. D., E. Huber, and C. C. Haudenschild. 1983. Mechanisms of destruction of Aspergillus fumigatus hyphae mediated by human monocytes. J. Infect. Dis. 147:474-483.
Diamond, R. D., R. Krzesicki, B. Epstein, and W. Jao. 1978. Damage to hyphal forms of fungi by human leukocytes in vitro: a possible host defense mechanism in aspergillosis and mucormycosis. Am. J. Pathol. 91:313-328.
Espinel-Ingroff, A. 2001. In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi. J. Clin. Microbiol. 39:954-958.
Espinel-Ingroff, A., M. Bartlett, R. Bowden, N. X. Chin, C. Cooper, A. Fothergill, M. R. McGinnis, P. Menezes, S. A. Messer, P. W. Nelson, F. C. Odds, L. Pasarell, J. Peter, M. A. Pfaller, J. H. Rex, M. G. Rinaldi, G. S. Shankland, T. J. Walsh, and I. Weitzman. 1997. Multicenter evaluation of proposed standardized procedure for antifungal susceptibility testing of filamentous fungi. J. Clin. Microbiol. 35:139-143.
Espinel-Ingroff, A., K. Dawson, M. Pfaller, E. Anaissie, B. Breslin, D. Dixon, A. Fothergill, V. Paetznick, J. Peter, and M. Rinaldi. 1995. Comparative and collaborative evaluation of standardization of antifungal susceptibility testing for filamentous fungi. Antimicrob. Agents Chemother. 39:314-319.
Ezekowitz, R. A., D. J. Williams, H. Koziel, M. Y. Armstrong, A. Warner, F. F. Richards, and R. M. Rose. 1991. Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor. Nature 351:155-158.
Gil-Lamaignere, C., A. Maloukou, J. L. Rodriguez-Tudela, and E. Roilides. 2001. Human phagocytic cell responses against Scedosporium prolificans. Med. Mycol. 39:169-175.
Hampton, M. B., A. J. Kettle, and C. C. Winterbourn. 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:3007-3017.
Higazi, A. A., T. Nassar, T. Ganz, D. J. Rader, R. Udassin, K. Bdeir, E. Hiss, B. S. Sachais, K. J. Williams, E. Leitersdorf, and D. B. Cines. 2000. The alpha-defensins stimulate proteoglycan-dependent catabolism of low-density lipoprotein by vascular cells: a new class of inflammatory apolipoprotein and a possible contributor to atherogenesis. Blood 96:1393-1398.
Jabado, N., J. L. Casanova, E. Haddad, F. Dulieu, J. C. Fournet, B. Dupont, A. Fischer, C. Hennequin, and S. Blanche. 1998. Invasive pulmonary infection due to Scedosporium apiospermum in two children with chronic granulomatous disease. Clin. Infect. Dis. 27:1437-1441.
Karbassi, A., J. M. Becker, J. S. Foster, and R. N. Moore. 1987. Enhanced killing of Candida albicans by murine macrophages treated with macrophage colony-stimulating factor: evidence for augmented expression of mannose receptors. J. Immunol. 139:417-421.
Kiraz, N., Z. Gulbas, Y. Akgun, and O. Uzun. 2001. Lymphadenitis caused by Scedosporium apiospermum in an immunocompetent patient. Clin. Infect. Dis. 32:E59-E61.
Kusne, S., S. Ariyanayagam-Baksh, D. C. Strollo, and J. Abernethy. 2000. Invasive Scedosporium apiospermum infection in a heart transplant recipient presenting with multiple skin nodules and a pulmonary consolidation. Transpl. Infect. Dis. 2:194-196.
Lesuisse, E., M. Casteras-Simon, and P. Labbe. 1996. Evidence for the Saccharomyces cerevisiae ferrireductase system being a multicomponent electron transport chain. J. Biol. Chem. 271:13578-13583.
Lyman, C. A., E. R. Simons, D. A. Melnick, and R. D. Diamond. 1988. Induction of signal transduction in human neutrophils by Candida albicans hyphae: the role of pertussis toxin-sensitive guanosine triphosphate-binding proteins. J. Infect. Dis. 158:1056-1064.
Meletiadis, J., J. F. Meis, J. W. Mouton, J. L. Rodriquez-Tudela, J. P. Donnelly, and P. E. Verweij. 2002. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob. Agents Chemother. 46:62-68.
Montero, A., J. E. Cohen, M. A. Fernandez, G. Mazzolini, C. R. Gomez, and J. Perugini. 1998. Cerebral pseudallescheriasis due to Pseudallescheria boydii as the first manifestation of AIDS. Clin. Infect. Dis. 26:1476-1477.
National Committee for Clinical Laboratory Standards. 1998. Reference method for broth dilution antifungal susceptibility testing of conidium-forming filamentous fungi; proposed standard M38-A. National Committee for Clinical Laboratory Standards, Wayne, Pa.
Ramanathan, B., E. G. Davis, C. R. Ross, and F. Blecha. 2002. Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes Infect. 4:361-372.
Roilides, E., A. Dimitriadou, I. Kadiltsoglou, T. Sein, J. Karpouzas, P. A. Pizzo, and T. J. Walsh. 1997. IL-10 exerts suppressive and enhancing effects on antifungal activity of mononuclear phagocytes against Aspergillus fumigatus. J. Immunol. 158:322-329.
Roilides, E., A. Holmes, C. Blake, D. Venzon, P. A. Pizzo, and T. J. Walsh. 1994. Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-γ. J. Infect. Dis. 170:894-899.
Roilides, E., H. Katsifa, and T. J. Walsh. 1998. Pulmonary host defences against Aspergillus fumigatus. Res. Immunol. 149:454-465.
Rollot, F., P. Blanche, B. Richaud-Thiriez, F. Le Pimpec-Barthes, M. Riquet, D. Dusser, D. Salmon, and D. Sicard. 2000. Pneumonia due to Scedosporium apiospermum in a patient with HIV infection. Scand. J. Infect. Dis. 32:439.
Schaffner, A., H. Douglas, and A. Braude. 1982. Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus: observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J. Clin. Investig. 69:617-631.
Sokol-Anderson, M. L., J. Brajtburg, and G. Medoff. 1986. Amphotericin B-induced oxidative damage and killing of Candida albicans. J. Infect. Dis. 154:76-83.
Stehle, S. E., R. A. Rogers, A. G. Harmsen, and R. A. Ezekowitz. 2000. A soluble mannose receptor immunoadhesin enhances phagocytosis of Pneumocystis carinii by human polymorphonuclear leukocytes in vitro. Scand. J. Immunol. 52:131-137.
Suzuki, T., N. Ohno, Y. Ohshima, and T. Yadomae. 1998. Soluble mannan and beta-glucan inhibit the uptake of Malassezia furfur by human monocytic cell line, THP-1. FEMS Immunol. Med. Microbiol. 21:223-230.
Tadros, T. S., K. A. Workowski, R. J. Siegel, S. Hunter, and D. A. Schwartz. 1998. Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydü): an emerging mycosis. Hum. Pathol. 29:1266-1272.
Tan, A. S., and M. V. Berridge. 2000. Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents. J. Immunol. Methods 238:59-68.
Wagner, D. K., C. Collins-Lech, and P. G. Sohnle. 1986. Inhibition of neutrophil killing of Candida albicans pseudohyphae by substances which quench hypochlorous acid and chloramines. Infect. Immun. 51:731-735.
Waldorf, A. 1989. Pulmonary defense mechanisms against opportunistic fungal pathogens. Immunol. Ser. 47:243-271.
Walenkamp, A. M., J. Scharringa, F. M. Schramel, F. E. Coenjaerts, and I. M. Hoepelman. 2000. Quantitative analysis of phagocytosis of Cryptococcus neoformans by adherent phagocytic cells by fluorescence multi-well plate reader. J. Microbiol. Methods 40:39-45.
Walsh, T. J., J. Peter, D. A. McGough, A. W. Fothergill, M. G. Rinaldi, and P. A. Pizzo. 1995. Activities of amphotericin B and antifungal azoles alone and in combination against Pseudallescheria boydii. Antimicrob. Agents Chemother. 39:1361-1364.
Washburn, R. G., J. I. Gallin, and J. E. Bennett. 1987. Oxidative killing of Aspergillus fumigatus proceeds by parallel myeloperoxidase-dependent and -independent pathways. Infect. Immun. 55:2088-2092.
Wright, S. D., and S. C. Silverstein. 1984. Phagocytosing macrophages exclude proteins from the zones of contact with opsonized targets. Nature 309:359-361.
Wu, Z., H. Ying, S. Yiu, J. Irvine, and R. Smith. 2002. Fungal keratitis caused by Scedosporium apiospermum. Report of two cases and review of treatment. Cornea 21:519-523.
Wysong, D. R., L. Christin, A. M. Sugar, P. W. Robbins, and R. D. Diamond. 1998. Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect. Immun. 66:1953-1961.
Yang, D., A. Biragyn, L. W. Kwak, and J. J. Oppenheim. 2002. Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 23:291-296.
