Fungi are microorganisms ubiquitous in our daily living. While most fungi pose little threat to human health, some, which are classified as pathogenic fungi can cause opportunistic infection in human. Opportunistic fungal pathogens infect human with primary or acquired immunodeficiency as a result of radiotherapy, chemotherapy, hematological disorders or human immunodeficiency virus (HIV) infection (Guarro, GeneJ et al. 1999). As a member of the genus Penicillium, which is most noted for the importance in food and drug production, P. marneffei is an opportunistic pathogen which infects immunocompromised patients particularly HIV positive patients. Invasive aspergillosis (IA) is a fatal disease caused by fungi of the Aspergillus genus in immunocompromised host. A. fumigatus, A. flavus and A. terrus are the three species that most commonly cause mycosis in immunocompromised hosts. In immunocompetent hosts, Aspergillus species cause selflimiting diffuse pneumonitis after massive spore inhalation or aspergilloma in patient with preexisting chronic lung diseases (Denning ; Denning and Stevens 1990).
Characterization of a novel virulence factor in Penicillium marneffei and Aspergillus fumigatus Doctor of Philosophy Thesis Tung Tsz Kwong The University of Hong Kong August 2011 Abstract of thesis entitled “Characterization of a novel virulence factor in Penicillium marneffei and Aspergillus fumigatus” Submitted by Tung Tsz Kwong for the degree of Doctor of Philosophy at The University of Hong Kong in August 2011 MP1, a gene previously identified in P marneffei by cDNA library screening, encodes a secreted cell wall mannoprotein Mp1p Thirteen MP1 homologues named MPLP1 to 13 were previously identified in P marneffei by BLAST analysis Two MP1 homologues namely AFMP1 and AFMP2 which encodes Afmp1p and Afmp2p were previously identified by expressed sequence tag library screening in Aspergillus fumigatus – an important fungal pathogen closely related to P marneffei Mp1p, Afmp1p and Afmp2p have previously been reported to be immunogenic Mp1p was also reported to bind fatty acid and was suggested to contribute to virulence in a MP1 knockout P marneffei strain in a mouse model and a cell line model although the Koch’s postulates has yet been met to establish MP1 as a novel virulence factor With reference to sequence identity of Afmp proteins to Mp1p, Afmp proteins were speculated to have functions similar to Mp1p BLAST searches against the A fumigatus genome identified two novel AFMPs namely AFMP3 and AFMP4 Sequence analysis of Afmp3p and Afmp4p revealed the presence of putative N-terminal signal peptide and substantial sequence identity to Mp1p, Afmp1p and Afmp2p Two MP1 knockdown P marneffei mutants were constructed to demonstrate suppression of MP1 expression alone can result in loss of virulence and also the dosage effect of MP1 expression on P marneffei virulence towards mice Subsequent mice challenge experiments using MP1 like protein (MPLP) knockdown strains suggested MP1 to be the most important virulence factor among all its homologues in P marneffei Histopathology examinations of organs from challenged mice suggested survival disadvantages in mice for P marneffei mutants with knockdown of MP1 and effect of MP1 on granuloma formation in infected mice Mice challenge experiments using AFMP1 to knockdown A fumgiatus mutants suggested significant decrease in virulence of A fumigatus upon AFMP4 knockdown and complete protection of challenged mice upon knockdown of AFMP1 to Histopathology examinations of organs from challenged mice suggested survival disadvantages in mice for A fumigatus mutants with knockdown of AFMPs and effect of AFMPs on granuloma formation in infected mice Mice experiments using Pichia pastoris expressing MP1 or AFMP4 suggested the effects of MP1 and AFMP4 on virulence are not caused by factors specific to P marneffei or A fumigatus It was shown using a human peripheral blood mononuclear cells model that Mp1p and Afmp4p confer intracellular survival advantage to P marneffei and A fumigatus upon infection Expression of Mp1p or Afmp4p in P pastoris also confers survival advantage to this nonpathogenic yeast in human peripheral blood mononuclear cells Reduction in proinflammatory prostaglandin E2 production were noticed in human peripheral blood mononuclear cells infected by P marneffei, A fumigatus or P pastoris strains that expressed Mp1p or Afmp4p Such reduction in eicosanoids production also coincides with the inhibition of apoptosis as shown by enzyme activity of caspase-8, caspase-9 and caspase-3 in human peripheral blood mononuclear cells These findings suggest two novel virulence factors – Mp1p and Afmp4p, which confer survival advantages to P marneffei and A fumigatus respectively (497 words) Characterization of a novel virulence factor in Penicillium marneffei and Aspergillus fumigatus by Tung Tsz Kwong B Sc (HK) A thesis submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy at The University of Hong Kong August 2011 Declaration I, Tung Tsz Kwong, declare that this thesis represents my own work, except where due acknowledgement is made, and that it has not been submitted to this or other institutions in application for a degree, diploma or any other qualifications Tung Tsz Kwong i Acknowledgements None of this would have been possible without the generous help of many people and tremendous luck I offer my gratitude to all my teachers, in particular, Prof Patrick Woo for his enlightenments and his tolerance of such a mediocre and reckless student I would like to express my gratitude to everyone who shared their valuable time and knowledge with me particularly Prof KY Yuen, Dr Susanna Lau and Dr Herman Tse Special thanks to Dr Ken Chong who equipped me with all the basics of mycology; Mr Andy Leung and Mr Timothy Cheng who I learnt most of my laboratory techniques from; every one of the fungal team especially Ms Apple Leung, Ms Emily Tam and Mr Franklin Chow for their support and assistance in all the difficult times; Dr Rex Au-Yeung for his help with histological examinations; Mr Jian-piao Cai who helped tremendously in generation of Pichia clones; all helpful collaborators; my friends and colleagues And may I express my deepest gratitude to my family and to all who loved me ii Contents Declaration i Acknowledgements ii Contents iii List of figures ix List of tables xii Abbreviations xiii Symbols xv Chapter Introduction 1.1 Penicillium marneffei and Aspergillus fumigatus as emerging pathogenic fungi 1.2 Classification of Penicillium marneffei and Aspergillus fumigatus 1.3 Penicillium marneffei 1.3.1 Mycology of Penicillium marneffei 1.3.1.1 Thermal dimorphism 1.3.1.2 Mould phase of Penicillium marneffei 1.3.1.3 Yeast phase of Penicillium marneffei 1.3.2 Ecology and epidemiology of Penicillium marneffei 10 1.3.2.1 Reservoirs 10 1.3.2.2 Route of transmission 11 1.3.2.3 Seasonal variation of Penicillium marneffei infections 12 1.3.2.4 Geographical variation of Penicillium marneffei 12 1.3.2.5 Risk factors 14 iii 1.3.3 Pathology, pathogenesis and immunology of Penicillium marneffei 16 1.3.3.1 Conidial adhesion 16 1.3.3.2 Immunology and evasion from host immunity 17 1.3.3.2.1 Role of innate immunity 17 1.3.3.2.2 Role of adaptive immunity 21 1.3.3.2.3 Evasion from host immunity 21 1.3.3.3 Toxins and virulence factors 23 1.3.3.4 Pathology 24 1.3.4 Treatment of penicilliosis 26 1.3.5 Prevention of penicilliosis 27 1.4 Aspergillus fumigatus 29 1.4.1 Mycology of Aspergillus fumigatus 29 1.4.2 Ecology and epidemiology of Aspergillus fumigatus 31 1.4.2.1 Reservoirs 31 1.4.2.2 Route of transmission 31 1.4.2.3 Risk factors 32 1.4.3 Pathology, pathogenesis and immunology of Aspergillus fumigatus 1.4.3.1 Immunology and evasion from host immunity 34 34 1.4.3.1.1 Role of innate immunity 34 1.4.3.1.2 Role of adaptive immunity 36 1.4.3.1.3 Evasion from host immunity 37 1.4.3.2 Toxins and virulence factors 1.4.3.2.1 Reactive oxygen species scavengers 38 38 iv 1.4.3.2.2 Transcription factors 39 1.4.3.2.3 Growth related factors 40 1.4.3.2.4 Secondary metabolites 40 1.4.3.3 Pathology 42 1.4.4 Treatment of aspergillosis 44 1.4.5 Prevention of aspergillosis 46 1.5 The antigenic mannoprotein superfamily 48 1.5.1 Mannoprotein (MP1) in Penicillium marneffei and Aspergillus fumigatus mannoprotein (AFMP) 1.5.2 Mp1p like protein in Penicillium marneffei 1.6 Rationale and scope of present studys Chapter Materials and methods 48 51 52 54 2.1 Fungal strains 54 2.2 DNA extraction 54 2.3 RNA extraction and reverse transcription 55 2.4 PCR amplification and sequencing 57 2.5 Identification and characterization of homologues of Mp1p in A fumigatus 59 2.6 Phylogenetic analysis 60 2.7 Plasmids construction 61 2.7.1 Construction of plasmids for gene knockout 61 2.7.2 Construction of plasmids for gene knockdown 65 2.7.3 Construction of plasmids for protein expression 75 2.8 Fungal transformation and screening for mutants 2.8.1 P marneffei transformation 78 78 v C Andres-Lacueva, U Senin and J M Guralnik (2006) "Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers." J Clin Endocrinol Metab 91(2): 439-446 Finkel-Jimenez, B., M Wuthrich, T Brandhorst and B S Klein (2001) "The WI-1 adhesin blocks phagocyte TNF-alpha production, imparting pathogenicity on Blastomyces dermatitidis." J Immunol 166(4): 2665-2673 Fisher, M C., W P Hanage, S de Hoog, E Johnson, M D Smith, N J White and N Vanittanakom (2005) "Low effective dispersal of asexual genotypes in heterogeneous landscapes by the endemic pathogen Penicillium marneffei." PLoS Pathog 1(2): e20 Fridkin, S K and W R Jarvis (1996) "Epidemiology of nosocomial fungal infections." Clinical microbiology reviews 9(4): 499-511 Funk, C D (2001) "Prostaglandins and leukotrienes: advances in eicosanoid biology." Science 294(5548): 1871-1875 Garcia-Rivera, J and A Casadevall (2001) "Melanization of Cryptococcus neoformans reduces its susceptibility to the antimicrobial effects of silver nitrate." Med Mycol 39(4): 353-357 Garlanda, C., E Hirsch, S Bozza, A Salustri, M De Acetis, R Nota, A Maccagno, F Riva, B Bottazzi, G Peri, A Doni, L Vago, M Botto, R De Santis, P Carminati, G Siracusa, F Altruda, A Vecchi, L Romani and A Mantovani (2002) "Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response." Nature 420(6912): 182-186 Graham, S C., M W Bahar, S Cooray, R A Chen, D M Whalen, N G Abrescia, D Alderton, R J Owens, D I Stuart, G L Smith and J M Grimes (2008) "Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis." PLoS Pathog 4(8): e1000128 Granger, D L., J B Hibbs, Jr and L M Broadnax (1991) "Urinary nitrate excretion in relation to murine macrophage activation Influence of dietary L-arginine and oral NG-monomethyl-L-arginine." J Immunol 146(4): 1294-1302 Green, S J., R M Crawford, J T Hockmeyer, M S Meltzer and C A Nacy (1990) "Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha." J Immunol 145(12): 4290-4297 Green, S J., S Mellouk, S L Hoffman, M S Meltzer and C A Nacy (1990) "Cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from L-arginine by macrophages and hepatocytes." Immunol Lett 25(1-3): 15-19 Green, S J., C A Nacy and M S Meltzer (1991) "Cytokine-induced synthesis of nitrogen oxides in macrophages: a protective host response to Leishmania and other intracellular pathogens." J Leukoc Biol 50(1): 93-103 Guarro, J., GeneJ and A M Stchigel (1999) "Developments in fungal taxonomy." Clinical microbiology reviews 12(3): 454-500 Gugnani, H., M C Fisher, A Paliwal-Johsi, N Vanittanakom, I Singh and P S Yadav (2004) "Role of Cannomys badius as a natural animal host of Penicillium marneffei in India." J Clin Microbiol 42(11): 5070-5075 Gupta, R and S Brunak (2002) "Prediction of glycosylation across the human proteome and the correlation to protein function." Pac Symp Biocomput: 310-322 Gupta Ramnee, J E., Brunak Soren (2004) "Prediction of N-glycosylation sites in human proteins." In preparation 174 Haase, A T (2005) "Perils at mucosal front lines for HIV and SIV and their hosts." Nat Rev Immunol 5(10): 783-792 Haines, J (1995) "Aspergillus in compost: straw man or fatal flaw Biocycle 6, 32-35." Hajjeh, R A and D W Warnock (2001) "Counterpoint: invasive aspergillosis and the environment rethinking our approach to prevention." Clin Infect Dis 33(9): 1549-1552 Hamilton, A J., L Jeavons, S Youngchim and N Vanittanakom (1999) "Recognition of fibronectin by Penicillium marneffei conidia via a sialic acid-dependent process and its relationship to the interaction between conidia and laminin." Infect Immun 67(10): 5200-5205 Hamilton, A J., L Jeavons, S Youngchim, N Vanittanakom and R J Hay (1998) "Sialic acid-dependent recognition of laminin by Penicillium marneffei conidia." Infect Immun 66(12): 6024-6026 Hay, R J (1993) "The prevention of invasive aspergillosis a realistic goal?" J Antimicrob Chemother 32(4): 515-517 Hector, R F., E Yee and M S Collins (1990) "Use of DBA/2N mice in models of systemic candidiasis and pulmonary and systemic aspergillosis." Infect Immun 58(5): 1476-1478 Hibbett, D S., M Binder, J F Bischoff, M Blackwell, P F Cannon, O E Eriksson, S Huhndorf, T James, P M Kirk, R Lucking, H Thorsten Lumbsch, F Lutzoni, P B Matheny, D J McLaughlin, M J Powell, S Redhead, C L Schoch, J W Spatafora, J A Stalpers, R Vilgalys, M C Aime, A Aptroot, R Bauer, D Begerow, G L Benny, L A Castlebury, P W Crous, Y C Dai, W Gams, D M Geiser, G W Griffith, C Gueidan, D L Hawksworth, G Hestmark, K Hosaka, R A Humber, K D Hyde, J E Ironside, U Koljalg, C P Kurtzman, K H Larsson, R Lichtwardt, J Longcore, J Miadlikowska, A Miller, J M Moncalvo, S Mozley-Standridge, F Oberwinkler, E Parmasto, V Reeb, J D Rogers, C Roux, L Ryvarden, J P Sampaio, A Schussler, J Sugiyama, R G Thorn, L Tibell, W A Untereiner, C Walker, Z Wang, A Weir, M Weiss, M M White, K Winka, Y J Yao and N Zhang (2007) "A higher-level phylogenetic classification of the Fungi." Mycol Res 111(Pt 5): 509-547 Hilmarsdottir, I., J L Meynard, O Rogeaux, G Guermonprez, A Datry, C Katlama, G Brucker, A Coutellier, M Danis and M Gentilini (1993) "Disseminated Penicillium marneffei infection associated with human immunodeficiency virus: a report of two cases and a review of 35 published cases." J Acquir Immune Defic Syndr 6(5): 466-471 Hissen, A H., A N Wan, M L Warwas, L J Pinto and M M Moore (2005) "The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence." Infect Immun 73(9): 5493-5503 Hoffman, P N., A M Bennett and G M Scott (1999) "Controlling airborne infections." J Hosp Infect 43 Suppl: S203-210 Horton, P and K Nakai (1997) "Better prediction of protein cellular localization sites with the k nearest neighbors classifier." Proc Int Conf Intell Syst Mol Biol 5: 147-152 Hsueh, P R., L J Teng, C C Hung, J H Hsu, P C Yang, S W Ho and K T Luh (2000) "Molecular evidence for strain dissemination of Penicillium marneffei: an emerging pathogen in Taiwan." J Infect Dis 181(5): 1706-1712 175 Huffnagle, G B., G B Toews, M D Burdick, M B Boyd, K S McAllister, R A McDonald, S L Kunkel and R M Strieter (1996) "Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans." J Immunol 157(10): 4529-4536 Hulshof, C M., R A van Zanten, J F Sluiters, M E van der Ende, R S Samson, P E Zondervan and J H Wagenvoort (1990) "Penicillium marneffei infection in an AIDS patient." Eur J Clin Microbiol Infect Dis 9(5): 370 Huynh, T X., H C Nguyen, H M Dinh Nguyen, M T Do, S Odermatt-Biays, A Degremont and D Malvy (2003) "[Penicillium marneffei infection and AIDS A review of 12 cases reported in the Tropical Diseases Centre, Ho Chi Minh City (Vietnam)]." Sante 13(3): 149-153 Ito, J I and J M Lyons (2002) "Vaccination of corticosteroid immunosuppressed mice against invasive pulmonary aspergillosis." J Infect Dis 186(6): 869-871 Jahn, B., A Koch, A Schmidt, G Wanner, H Gehringer, S Bhakdi and A A Brakhage (1997) "Isolation and characterization of a pigmentless-conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence." Infect Immun 65(12): 5110-5117 James, T Y., F Kauff, C L Schoch, P B Matheny, V Hofstetter, C J Cox, G Celio, C Gueidan, E Fraker, J Miadlikowska, H T Lumbsch, A Rauhut, V Reeb, A E Arnold, A Amtoft, J E Stajich, K Hosaka, G H Sung, D Johnson, B O'Rourke, M Crockett, M Binder, J M Curtis, J C Slot, Z Wang, A W Wilson, A Schussler, J E Longcore, K O'Donnell, S Mozley-Standridge, D Porter, P M Letcher, M J Powell, J W Taylor, M M White, G W Griffith, D R Davies, R A Humber, J B Morton, J Sugiyama, A Y Rossman, J D Rogers, D H Pfister, D Hewitt, K Hansen, S Hambleton, R A Shoemaker, J Kohlmeyer, B Volkmann-Kohlmeyer, R A Spotts, M Serdani, P W Crous, K W Hughes, K Matsuura, E Langer, G Langer, W A Untereiner, R Lucking, B Budel, D M Geiser, A Aptroot, P Diederich, I Schmitt, M Schultz, R Yahr, D S Hibbett, F Lutzoni, D J McLaughlin, J W Spatafora and R Vilgalys (2006) "Reconstructing the early evolution of Fungi using a six-gene phylogeny." Nature 443(7113): 818-822 Jayadev, S., C M Linardic and Y A Hannun (1994) "Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor alpha." J Biol Chem 269(8): 5757-5763 Jones, P D and J See (1992) "Penicillium marneffei infection in patients infected with human immunodeficiency virus: late presentation in an area of nonendemicity." Clin Infect Dis 15(4): 744 Julander, I and B Petrini (1997) "Penicillium marneffei infection in a Swedish HIV-infected immunodeficient narcotic addict." Scand J Infect Dis 29(3): 320-322 Kaldor, J M., W Sittitrai, T J John and T Kitamura (1994) "The emerging epidemic of HIV infection and AIDS in Asia and the Pacific." AIDS Suppl 2: S1-2 Kavanagh, K (2007) "New insights in medical mycology, Springer Netherlands: 304." Kendrick, B (2000) "The fifth kingdom New buryport Mass, Focus Pub: xii, 386." Knowles, M R and R C Boucher (2002) "Mucus clearance as a primary innate defense mechanism for mammalian airways." J Clin Invest 109(5): 571-577 Koch, R (1893) "Ueber den augenblicklichen Stand der bakteriologischen Choleradiagnose." Medical Microbiology and Immunology 14(1): 319-338 Kontoyiannis, D P and G P Bodey (2002) "Invasive aspergillosis in 2002: an 176 update." Eur J Clin Microbiol Infect Dis 21(3): 161-172 Krappmann, S., E M Bignell, U Reichard, T Rogers, K Haynes and G H Braus (2004) "The Aspergillus fumigatus transcriptional activator CpcA contributes significantly to the virulence of this fungal pathogen." Mol Microbiol 52(3): 785-799 Krasinski, K., R S Holzman, B Hanna, M A Greco, M Graff and M Bhogal (1985) "Nosocomial fungal infection during hospital renovation." Infect Control 6(7): 278-282 Kronauer, C M., G Schar, M Barben and H Buhler (1993) "[HIV-associated Penicillium marneffei infection]." Schweiz Med Wochenschr 123(9): 385-390 Kudeken, N., K Kawakami, N Kusano and A Saito (1996) "Cell-mediated immunity in host resistance against infection caused by Penicillium marneffei." J Med Vet Mycol 34(6): 371-378 Kudeken, N., K Kawakami and A Saito (1997) "CD4+ T cell-mediated fatal hyperinflammatory reactions in mice infected with Penicillium marneffei." Clin Exp Immunol 107(3): 468-473 Kudeken, N., K Kawakami and A Saito (1999) "Cytokine-induced fungicidal activity of human polymorphonuclear leukocytes against Penicillium marneffei." FEMS Immunol Med Microbiol 26(2): 115-124 Kudeken, N., K Kawakami and A Saito (2000) "Mechanisms of the in vitro fungicidal effects of human neutrophils against Penicillium marneffei induced by granulocyte-macrophage colony-stimulating factor (GM-CSF)." Clin Exp Immunol 119(3): 472-478 Kullberg, B J (1997) "Trends in immunotherapy of fungal infections." Eur J Clin Microbiol Infect Dis 16(1): 51-55 Kullberg, B J and J W van 't Wout (1994) "Cytokines in the treatment of fungal infections." Biotherapy 7(3-4): 195-210 Kuwayama, H., S Obara, T Morio, M Katoh, H Urushihara and Y Tanaka (2002) "PCR-mediated generation of a gene disruption construct without the use of DNA ligase and plasmid vectors." Nucleic Acids Res 30(2): E2 Kwon-Chung, K J., Schwartz, I S., Rybak, B J (1975) "A pulmonary fungus ball produced by Cladosporium cladosporioides 64, 564-568." Kwon-Chung, K J and J A Sugui (2009) "What we know about the role of gliotoxin in the pathobiology of Aspergillus fumigatus?" Med Mycol 47 Suppl 1: S97-103 Langfelder, K., B Jahn, H Gehringer, A Schmidt, G Wanner and A A Brakhage (1998) "Identification of a polyketide synthase gene (pksP) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence." Med Microbiol Immunol 187(2): 79-89 Langfelder, K., M Streibel, B Jahn, G Haase and A A Brakhage (2003) "Biosynthesis of fungal melanins and their importance for human pathogenic fungi." Fungal Genet Biol 38(2): 143-158 Laniado-Laborin, R (2007) "Coccidioidomycosis and other endemic mycoses in Mexico." Rev Iberoam Micol 24(4): 249-258 Larkin, M A., G Blackshields, N P Brown, R Chenna, P A McGettigan, H McWilliam, F Valentin, I M Wallace, A Wilm, R Lopez, J D Thompson, T J Gibson and D G Higgins (2007) "Clustal W and Clustal X version 2.0." Bioinformatics 23(21): 2947-2948 Latge, J P (1999) "Aspergillus fumigatus and aspergillosis." Clinical microbiology reviews 12(2): 310-350 177 Lau, C C Y (2008) "Characterization and application of MP1 homologues in Penicillium marneffei." Thesis, HKU Leal, S M., Jr., S Cowden, Y C Hsia, M A Ghannoum, M Momany and E Pearlman (2010) "Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis." PLoS Pathog 6: e1000976 Lee, N (2008) "Penicilliosis: an AIDS-defining disease in Asia." Hong Kong Med J 14(2): 88-89 Lentino, J R., M A Rosenkranz, J A Michaels, V P Kurup, H D Rose and M W Rytel (1982) "Nosocomial aspergillosis: a retrospective review of airborne disease secondary to road construction and contaminated air conditioners." Am J Epidemiol 116(3): 430-437 Lesk, A M and C Chothia (1980) "How Different Amino-Acid-Sequences Determine Similar Protein Structures - Structure and Evolutionary Dynamics of the Globins." Journal of Molecular Biology 136(3): 225-& Li, H., H Zhou, Y Luo, H Ouyang, H Hu and C Jin (2007) "Glycosylphosphatidylinositol (GPI) anchor is required in Aspergillus fumigatus for morphogenesis and virulence." Mol Microbiol 64(4): 1014-1027 Liao, S., E T Tung, W Zheng, K Chong, Y Xu, P Dai, Y Guo, M Bartlam, K Y Yuen and Z Rao (2010) "Crystal structure of the Mp1p ligand binding domain reveals its function as a fatty acid-binding protein." J Biol Chem 285(12): 9211-9220 Liebmann, B., M Muller, A Braun and A A Brakhage (2004) "The cyclic AMP-dependent protein kinase a network regulates development and virulence in Aspergillus fumigatus." Infect Immun 72(9): 5193-5203 Lo, Y., K Tintelnot, U Lippert and T Hoppe (2000) "Disseminated Penicillium marneffei infection in an African AIDS patient." Trans R Soc Trop Med Hyg 94(2): 187 Low, L S S (2002) "The Pattern of AIDS Reporting and the Implications on HIV Surveillance." Public Health and Epidemiology Bulletin 11(4) Lu, M L., M Sato, B Cao and J P Richie (1996) "UV irradiation-induced apoptosis leads to activation of a 36-kDa myelin basic protein kinase in HL-60 cells." Proc Natl Acad Sci U S A 93(17): 8977-8982 Luh, K T (1998) "Penicillium marneffei fungemia in an AIDS patient: the first case report in Taiwan." Changgeng Yi Xue Za Zhi 21(3): 362 Lupi, O., S K Tyring and M R McGinnis (2005) "Tropical dermatology: fungal tropical diseases." J Am Acad Dermatol 53(6): 931-951, quiz 952-934 Madan, T., P Eggleton, U Kishore, P Strong, S S Aggrawal, P U Sarma and K B Reid (1997) "Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages." Infect Immun 65(8): 3171-3179 Marr, K A., R A Carter, M Boeckh, P Martin and L Corey (2002) "Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors." Blood 100(13): 4358-4366 Martchenko, M., A M Alarco, D Harcus and M Whiteway (2004) "Superoxide dismutases in Candida albicans: transcriptional regulation and functional characterization of the hyphal-induced SOD5 gene." Mol Biol Cell 15(2): 456-467 McDonagh, A., N D Fedorova, J Crabtree, Y Yu, S Kim, D Chen, O Loss, T Cairns, G Goldman, D Armstrong-James, K Haynes, H Haas, M Schrettl, G 178 May, W C Nierman and E Bignell (2008) "Sub-telomere directed gene expression during initiation of invasive aspergillosis." PLoS Pathog 4(9): e1000154 Mehrad, B., R M Strieter and T J Standiford (1999) "Role of TNF-alpha in pulmonary host defense in murine invasive aspergillosis." J Immunol 162(3): 1633-1640 Mellado, E., A Aufauvre-Brown, N A Gow and D W Holden (1996) "The Aspergillus fumigatus chsC and chsG genes encode class III chitin synthases with different functions." Mol Microbiol 20(3): 667-679 Montaner LJ, C M., Herbein G (1996) "Human monocytes: isolation, cultivation, and its applications." Herzenberg LA, ed Weir’s handbook of experimental immunology 5th ed Vol IV Cambridge, MA: Blackwell Science.: 1-11 Moreno, M A., O Ibrahim-Granet, R Vicentefranqueira, J Amich, P Ave, F Leal, J P Latge and J A Calera (2007) "The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence." Mol Microbiol 64(5): 1182-1197 Morris-Jones, R., S Youngchim, B L Gomez, P Aisen, R J Hay, J D Nosanchuk, A Casadevall and A J Hamilton (2003) "Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection." Infect Immun 71(7): 4026-4033 Mouyna, I., W Morelle, M Vai, M Monod, B Lechenne, T Fontaine, A Beauvais, J Sarfati, M C Prevost, C Henry and J P Latge (2005) "Deletion of GEL2 encoding for a beta(1-3)glucanosyltransferase affects morphogenesis and virulence in Aspergillus fumigatus." Mol Microbiol 56(6): 1675-1688 Muhlemann, K., C Wenger, R Zenhausern and M G Tauber (2005) "Risk factors for invasive aspergillosis in neutropenic patients with hematologic malignancies." Leukemia 19(4): 545-550 Mullbacher, A and R D Eichner (1984) "Immunosuppression in vitro by a metabolite of a human pathogenic fungus." Proc Natl Acad Sci U S A 81(12): 3835-3837 Murray, H W (1992) "The interferons, macrophage activation, and host defense against nonviral pathogens." J Interferon Res 12(5): 319-322 Nakamura, K., A Miyazato, Y Koguchi, Y Adachi, N Ohno, S Saijo, Y Iwakura, K Takeda, S Akira, J Fujita, K Ishii, M Kaku and K Kawakami (2008) "Toll-like receptor (TLR2) and dectin-1 contribute to the production of IL-12p40 by bone marrow-derived dendritic cells infected with Penicillium marneffei." Microbes Infect 10(10-11): 1223-1227 Nakayashiki, H., S Hanada, B Q Nguyen, N Kadotani, Y Tosa and S Mayama (2005) "RNA silencing as a tool for exploring gene function in ascomycete fungi." Fungal Genet Biol 42(4): 275-283 Nicholson, W J., J Slight and K Donaldson (1996) "Inhibition of the transcription factors NF-kappa B and AP-1 underlies loss of cytokine gene expression in rat alveolar macrophages treated with a diffusible product from the spores of Aspergillus fumigatus." Am J Respir Cell Mol Biol 15(1): 88-96 Nierman, W C., A Pain, M J Anderson, J R Wortman, H S Kim, J Arroyo, M Berriman, K Abe, D B Archer, C Bermejo, J Bennett, P Bowyer, D Chen, M Collins, R Coulsen, R Davies, P S Dyer, M Farman, N Fedorova, T V Feldblyum, R Fischer, N Fosker, A Fraser, J L Garcia, M J Garcia, A Goble, G H Goldman, K Gomi, S Griffith-Jones, R Gwilliam, B Haas, H Haas, D Harris, H Horiuchi, J Huang, S Humphray, J Jimenez, N Keller, H 179 Khouri, K Kitamoto, T Kobayashi, S Konzack, R Kulkarni, T Kumagai, A Lafon, J P Latge, W Li, A Lord, C Lu, W H Majoros, G S May, B L Miller, Y Mohamoud, M Molina, M Monod, I Mouyna, S Mulligan, L Murphy, S O'Neil, I Paulsen, M A Penalva, M Pertea, C Price, B L Pritchard, M A Quail, E Rabbinowitsch, N Rawlins, M A Rajandream, U Reichard, H Renauld, G D Robson, S Rodriguez de Cordoba, J M Rodriguez-Pena, C M Ronning, S Rutter, S L Salzberg, M Sanchez, J C Sanchez-Ferrero, D Saunders, K Seeger, R Squares, S Squares, M Takeuchi, F Tekaia, G Turner, C R Vazquez de Aldana, J Weidman, O White, J Woodward, J H Yu, C Fraser, J E Galagan, K Asai, M Machida, N Hall, B Barrell and D W Denning (2005) "Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus." Nature 438(7071): 1151-1156 O'Gorman, C M., H T Fuller and P S Dyer (2009) "Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus." Nature 457(7228): 471-474 Offner, F (1997) "Hematopoietic growth factors in cancer patients with invasive fungal infections." Eur J Clin Microbiol Infect Dis 16(1): 56-63 Panackal, A A., H Li, D P Kontoyiannis, M Mori, C A Perego, M Boeckh and K A Marr (2010) "Geoclimatic influences on invasive aspergillosis after hematopoietic stem cell transplantation." Clin Infect Dis 50(12): 1588-1597 Panepinto, J C., B G Oliver, T W Amlung, D S Askew and J C Rhodes (2002) "Expression of the Aspergillus fumigatus rheb homologue, rhbA, is induced by nitrogen starvation." Fungal Genet Biol 36(3): 207-214 Panepinto, J C., B G Oliver, J R Fortwendel, D L Smith, D S Askew and J C Rhodes (2003) "Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein RhbA reduces virulence in a model of Invasive pulmonary aspergillosis." Infect Immun 71(5): 2819-2826 Paris, S., J P Debeaupuis, R Crameri, M Carey, F Charles, M C Prevost, C Schmitt, B Philippe and J P Latge (2003) "Conidial hydrophobins of Aspergillus fumigatus." Appl Environ Microbiol 69(3): 1581-1588 Park, S J and B Mehrad (2009) "Innate immunity to Aspergillus species." Clinical microbiology reviews 22(4): 535-551 Pathak, A., F D Pien and L Carvalho (1998) "Amphotericin B use in a community hospital, with special emphasis on side effects." Clin Infect Dis 26(2): 334-338 Patterson, T F (1998) "Approaches to therapy for invasive mycoses the role of amphotericin B." Clin Infect Dis 26(2): 339-340 Patterson, T F., Kirkpatrick, W R., White, M., Hiemenz, J W., Wingard, J R., Dupont, B., Rinaldi, M G., Stevens, D A & Graybill, J R (2000) "Invasive aspergillosis Disease spectrum, treatment practices, and outcomes I3 Aspergillus Study Group." Medicine (Baltimore) 79: 250-260 Perlman, D C and J Carey (2006) "Prevention of Disseminated Penicillium marneffei in human immunodeficiency virus-infected Travelers." J Travel Med 13(6): 386; author reply 387 Perruccio, K., A Tosti, E Burchielli, F Topini, L Ruggeri, A Carotti, M Capanni, E Urbani, A Mancusi, F Aversa, M F Martelli, L Romani and A Velardi (2005) "Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation." Blood 106(13): 4397-4406 Peto, T E., R Bull, P R Millard, D W Mackenzie, C K Campbell, M E Haines 180 and R G Mitchell (1988) "Systemic mycosis due to Penicillium marneffei in a patient with antibody to human immunodeficiency virus." J Infect 16(3): 285-290 Philippe, B., O Ibrahim-Granet, M C Prevost, M A Gougerot-Pocidalo, M Sanchez Perez, A Van der Meeren and J P Latge (2003) "Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates." Infect Immun 71(6): 3034-3042 Piehl, M R., R L Kaplan and M H Haber (1988) "Disseminated penicilliosis in a patient with acquired immunodeficiency syndrome." Arch Pathol Lab Med 112(12): 1262-1264 Pihet, M., P Vandeputte, G Tronchin, G Renier, P Saulnier, S Georgeault, R Mallet, D Chabasse, F Symoens and J P Bouchara (2009) "Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia." BMC Microbiol 9: 177 Piomelli, D (2002) "Arachidonic acid." Neuropsychopharmacology: The Fifth Generation of Progress: An Official Publication of the American College of Neuropsychopharmacology Piva, T J (1994) "Gliotoxin induces apoptosis in mouse L929 fibroblast cells." Biochem Mol Biol Int 33(3): 411-419 Poggeler, S (2002) "Genomic evidence for mating abilities in the asexual pathogen Aspergillus fumigatus." Curr Genet 42(3): 153-160 Polak, A (1990) "Melanin as a virulence factor in pathogenic fungi." Mycoses 33(5): 215-224 Pongpom, M and N Vanittanakom (2011) "Characterization of an MPLP6, a gene coding for a yeast phase specific, antigenic mannoprotein in Penicillium marneffei." Med Mycol 49(1): 32-39 Pongpom, P., C R Cooper, Jr and N Vanittanakom (2005) "Isolation and characterization of a catalase-peroxidase gene from the pathogenic fungus, Penicillium marneffei." Med Mycol 43(5): 403-411 Potera, C (2001) "Clothing spreads spores." Environ Health Perspect 109(8): A365 Powderly, W G., D Finkelstein, J Feinberg, P Frame, W He, C van der Horst, S L Koletar, M E Eyster, J Carey, H Waskin and et al (1995) "A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection NIAID AIDS Clinical Trials Group." N Engl J Med 332(11): 700-705 Prahl, P (1992) "Reduction of indoor airborne mould spores." Allergy 47(4 Pt 2): 362-365 Punt, P J., R P Oliver, M A Dingemanse, P H Pouwels and C A van den Hondel (1987) "Transformation of Aspergillus based on the hygromycin B resistance marker from Escherichia coli." Gene 56(1): 117-124 Ranjana, K H., K Priyokumar, T J Singh, C Gupta Ch, L Sharmila, P N Singh and A Chakrabarti (2002) "Disseminated Penicillium marneffei infection among HIV-infected patients in Manipur state, India." J Infect 45(4): 268-271 Rankin, N E (1953) "Disseminated aspergillosis and moniliasis associated with agranulocytosis and antibiotic therapy." Br Med J 1(4816): 918-919 Rechsteiner, M and S W Rogers (1996) "PEST sequences and regulation by proteolysis." Trends Biochem Sci 21(7): 267-271 Rex, J H., J E Bennett, J I Gallin, H L Malech and D A Melnick (1990) "Normal and deficient neutrophils can cooperate to damage Aspergillus 181 fumigatus hyphae." J Infect Dis 162(2): 523-528 Rhame, F S (1991) "Prevention of nosocomial aspergillosis." J Hosp Infect 18 Suppl A: 466-472 Riccardi, C and I Nicoletti (2006) "Analysis of apoptosis by propidium iodide staining and flow cytometry." Nat Protoc 1(3): 1458-1461 Robinson, B W., T J Venaille, A H Mendis and R McAleer (1990) "Allergens as proteases: an Aspergillus fumigatus proteinase directly induces human epithelial cell detachment." J Allergy Clin Immunol 86(5): 726-731 Rogers, S., R Wells and M Rechsteiner (1986) "Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis." Science 234(4774): 364-368 Roilides, E., C A Lyman, T Sein, R Petraitiene and T J Walsh (2003) "Macrophage colony-stimulating factor enhances phagocytosis and oxidative burst of mononuclear phagocytes against Penicillium marneffei conidia." FEMS Immunol Med Microbiol 36(1-2): 19-26 Romani, L (1999) "Immunity to Candida albicans: Th1, Th2 cells and beyond." Curr Opin Microbiol 2(4): 363-367 Rongrungruang, Y and S M Levitz (1999) "Interactions of Penicillium marneffei with human leukocytes in vitro." Infect Immun 67(9): 4732-4736 Rost, B and J Liu (2003) "The PredictProtein server." Nucleic Acids Res 31(13): 3300-3304 Rost, B., G Yachdav and J Liu (2004) "The PredictProtein server." Nucleic Acids Res 32(Web Server issue): W321-326 Rychly, D J and J T DiPiro (2005) "Infections associated with tumor necrosis factor-alpha antagonists." Pharmacotherapy 25(9): 1181-1192 Samson, R A (1994) "Taxonomy- current concepts of Aspergillus systematics." Biotechnology handbooks Aspergillus: 1-22 Samson, R A., Reenen-Hoekstra, V (1988) " Introduction to food-borne fungi." Sanchez-Martinez, C and J Perez-Martin (2001) "Dimorphism in fungal pathogens: Candida albicans and Ustilago maydis similar inputs, different outputs." Curr Opin Microbiol 4(2): 214-221 Sanglard, D., F Ischer, M Monod and J Bille (1996) "Susceptibilities of Candida albicans multidrug transporter mutants to various antifungal agents and other metabolic inhibitors." Antimicrob Agents Chemother 40(10): 2300-2305 Sar, B., S Boy, C Keo, C C Ngeth, N Prak, M Vann, D Monchy and J L Sarthou (2006) "In vitro antifungal-drug susceptibilities of mycelial and yeast forms of Penicillium marneffei isolates in Cambodia." J Clin Microbiol 44(11): 4208-4210 Sarubbi, F A., Jr., H B Kopf, M B Wilson, M R McGinnis and W A Rutala (1982) "Increased recovery of Aspergillus flavus from respiratory specimens during hospital construction." Am Rev Respir Dis 125(1): 33-38 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 Invest 69(3): 617-631 Schelenz, S., D A Smith and G J Bancroft (1999) "Cytokine and chemokine responses following pulmonary challenge with Aspergillus fumigatus: obligatory role of TNF-alpha and GM-CSF in neutrophil recruitment." Med Mycol 37(3): 183-194 Schnitzler, N., H Peltroche-Llacsahuanga, N Bestier, J Zundorf, R Lutticken and G Haase (1999) "Effect of melanin and carotenoids of Exophiala (Wangiella) 182 dermatitidis on phagocytosis, oxidative burst, and killing by human neutrophils." Infect Immun 67(1): 94-101 Schrettl, M., E Bignell, C Kragl, C Joechl, T Rogers, H N Arst, Jr., K Haynes and H Haas (2004) "Siderophore biosynthesis but not reductive iron assimilation is essential for Aspergillus fumigatus virulence." J Exp Med 200(9): 1213-1219 Schroder, K., P J Hertzog, T Ravasi and D A Hume (2004) "Interferon-gamma: an overview of signals, mechanisms and functions." J Leukoc Biol 75(2): 163-189 Schwartz, S and E Thiel (2003) "CNS-aspergillosis: are there new treatment options?" Mycoses 46 Suppl 2: 8-14 Segal, B H (2009) "Aspergillosis." N Engl J Med 360(18): 1870-1884 Segal, B H and L R Romani (2009) "Invasive aspergillosis in chronic granulomatous disease." Med Mycol 47 Suppl 1: S282-290 Segretain, G (1959) "[Penicillium marneffei n.sp., agent of a mycosis of the reticuloendothelial system]." Mycopathologia 11: 327-353 Shibuya, K., S Paris, T Ando, H Nakayama, T Hatori and J P Latge (2006) "Catalases of Aspergillus fumigatus and inflammation in aspergillosis." Nippon Ishinkin Gakkai Zasshi 47(4): 249-255 Sigler, L K., M J (1999) "Aspergillus, Fusarium, and other opportunistic moniliaceous fungi In Manual of Clinical microbiology, pp 1213-1241 Edited by P R Murray, E J Baron, M A Pfaller, F C Tenover & R H Yolken Washington: American Society of microbiology." Sirisanthana, T and K Supparatpinyo (1998) "Epidemiology and management of penicilliosis in human immunodeficiency virus-infected patients." Int J Infect Dis 3(1): 48-53 Sirisanthana, T., K Supparatpinyo, J Perriens and K E Nelson (1998) "Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients." Clin Infect Dis 26(5): 1107-1110 Sisto, F., A Miluzio, O Leopardi, M Mirra, J R Boelaert and D Taramelli (2003) "Differential cytokine pattern in the spleens and livers of BALB/c mice infected with Penicillium marneffei: protective role of gamma interferon." Infect Immun 71(1): 465-473 Sobottka, I., H Albrecht, D Mack, H J Stellbrink, J van Lunzen, K Tintelnot and R Laufs (1996) "Systemic Penicillium marneffei infection in a German AIDS patient." Eur J Clin Microbiol Infect Dis 15(3): 256-259 Soriani, F M., I Malavazi, M E da Silva Ferreira, M Savoldi, M R Von Zeska Kress, M H de Souza Goldman, O Loss, E Bignell and G H Goldman (2008) "Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA." Mol Microbiol 67(6): 1274-1291 Spikes, S., R Xu, C K Nguyen, G Chamilos, D P Kontoyiannis, R H Jacobson, D E Ejzykowicz, L Y Chiang, S G Filler and G S May (2008) "Gliotoxin production in Aspergillus fumigatus contributes to host-specific differences in virulence." J Infect Dis 197(3): 479-486 Srinoulprasert, Y., P Kongtawelert and S C Chaiyaroj (2006) "Chondroitin sulfate B and heparin mediate adhesion of Penicillium marneffei conidia to host extracellular matrices." Microb Pathog 40(3): 126-132 Stanzani, M., E Orciuolo, R Lewis, D P Kontoyiannis, S L Martins, L S St John and K V Komanduri (2005) "Aspergillus fumigatus suppresses the human 183 cellular immune response via gliotoxin-mediated apoptosis of monocytes." Blood 105(6): 2258-2265 Steele, C., R R Rapaka, A Metz, S M Pop, D L Williams, S Gordon, J K Kolls and G D Brown (2005) "The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus." PLoS Pathog 1(4): e42 Steinbach, W J., R A Cramer, Jr., B Z Perfect, Y G Asfaw, T C Sauer, L K Najvar, W R Kirkpatrick, T F Patterson, D K Benjamin, Jr., J Heitman and J R Perfect (2006) "Calcineurin controls growth, morphology, and pathogenicity in Aspergillus fumigatus." Eukaryot Cell 5(7): 1091-1103 Stergiopoulou, T., J Meletiadis, E Roilides, D E Kleiner, R Schaufele, M Roden, S Harrington, L Dad, B Segal and T J Walsh (2007) "Host-dependent patterns of tissue injury in invasive pulmonary aspergillosis." Am J Clin Pathol 127(3): 349-355 Stevens, D A (1999) "Itraconazole in cyclodextrin solution." Pharmacotherapy 19(5): 603-611 Streifel, A J., J L Lauer, D Vesley, B Juni and F S Rhame (1983) "Aspergillus fumigatus and other thermotolerant fungi generated by hospital building demolition." Appl Environ Microbiol 46(2): 375-378 Suen, Y K., K P Fung, C Y Lee and S K Kong (2001) "Gliotoxin induces apoptosis in cultured macrophages via production of reactive oxygen species and cytochrome c release without mitochondrial depolarization." Free Radic Res 35(1): 1-10 Sugui, J A., J Pardo, Y C Chang, K A Zarember, G Nardone, E M Galvez, A Mullbacher, J I Gallin, M M Simon and K J Kwon-Chung (2007) "Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone." Eukaryot Cell 6(9): 1562-1569 Sunyaev, S R., F Eisenhaber, I V Rodchenkov, B Eisenhaber, V G Tumanyan and E N Kuznetsov (1999) "PSIC: profile extraction from sequence alignments with position-specific counts of independent observations." Protein Eng 12(5): 387-394 Supparatpinyo, K., S Chiewchanvit, P Hirunsri, V Baosoung, C Uthammachai, B Chaimongkol and T Sirisanthana (1992) "An efficacy study of itraconazole in the treatment of Penicillium marneffei infection." J Med Assoc Thai 75(12): 688-691 Supparatpinyo, K., C Khamwan, V Baosoung, K E Nelson and T Sirisanthana (1994) "Disseminated Penicillium marneffei infection in southeast Asia." Lancet 344(8915): 110-113 Supparatpinyo, K., J Perriens, K E Nelson and T Sirisanthana (1998) "A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus." N Engl J Med 339(24): 1739-1743 Supparatpinyo, K and H T Schlamm (2007) "Voriconazole as therapy for systemic Penicillium marneffei infections in AIDS patients." Am J Trop Med Hyg 77(2): 350-353 Taborda, C P., M B da Silva, J D Nosanchuk and L R Travassos (2008) "Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview." Mycopathologia 165(4-5): 331-339 Tamura, K., D Peterson, N Peterson, G Stecher, M Nei and S Kumar (2011) "MEGA5: Molecular Evolutionary Genetics Analysis using Maximum 184 Likelihood, Evolutionary Distance, and Maximum Parsimony Methods." Mol Biol Evol Tanaka, E., S Ito-Kuwa, K Nakamura, S Aoki, V Vidotto and M Ito (2005) "Comparisons of the laccase gene among serotypes and melanin-deficient variants of Cryptococcus neoformans." Microbiol Immunol 49(3): 209-217 Tang, B S., J F Chan, M Chen, O T Tsang, M Y Mok, R W Lai, R Lee, T L Que, H Tse, I W Li, K K To, V C Cheng, E Y Chan, B Zheng and K Y Yuen (2010) "Disseminated penicilliosis, recurrent bacteremic nontyphoidal salmonellosis, and burkholderiosis associated with acquired immunodeficiency due to autoantibody against gamma interferon." Clin Vaccine Immunol 17(7): 1132-1138 Taramelli, D., S Brambilla, G Sala, A Bruccoleri, C Tognazioli, L Riviera-Uzielli and J R Boelaert (2000) "Effects of iron on extracellular and intracellular growth of Penicillium marneffei." Infect Immun 68(3): 1724-1726 Tavares, A H., S S Silva, V V Bernardes, A Q Maranhao, C M Kyaw, M Pocas-Fonseca and I Silva-Pereira (2005) "Virulence insights from the Paracoccidioides brasiliensis transcriptome." Genet Mol Res 4(2): 372-389 Teixeira, P A., R A De Castro, F R Ferreira, M M Cunha, A P Torres, C V Penha, S Rozental and L M Lopes-Bezerra (2010) "L-DOPA accessibility in culture medium increases melanin expression and virulence of Sporothrix schenckii yeast cells." Med Mycol 48(5): 687-695 Thirach, S., C R Cooper, Jr and N Vanittanakom (2008) "Molecular analysis of the Penicillium marneffei glyceraldehyde-3-phosphate dehydrogenase-encoding gene (gpdA) and differential expression of gpdA and the isocitrate lyase-encoding gene (acuD) upon internalization by murine macrophages." J Med Microbiol 57(Pt 11): 1322-1328 Thirach, S., C R Cooper, Jr., P Vanittanakom and N Vanittanakom (2007) "The copper, zinc superoxide dismutase gene of Penicillium marneffei: cloning, characterization, and differential expression during phase transition and macrophage infection." Med Mycol 45(5): 409-417 Thompson, J D., D G Higgins and T J Gibson (1994) "CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice." Nucleic Acids Res 22(22): 4673-4680 Tsunawaki, S., L S Yoshida, S Nishida, T Kobayashi and T Shimoyama (2004) "Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst NADPH oxidase." Infect Immun 72(6): 3373-3382 Udenfriend, S and K Kodukula (1995) "How glycosylphosphatidylinositol-anchored membrane proteins are made." Annu Rev Biochem 64: 563-591 UNAIDS (2007) "AIDS epidemic update 2007." VandenBergh, M F., P E Verweij and A Voss (1999) "Epidemiology of nosocomial fungal infections: invasive aspergillosis and the environment." Diagn Microbiol Infect Dis 34(3): 221-227 Vanittanakom, N., C R Cooper, Jr., M C Fisher and T Sirisanthana (2006) "Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects." Clinical microbiology reviews 19(1): 95-110 Vanittanakom, N., M Mekaprateep, P Sriburee, P Vanittanakom and P Khanjanasthiti (1995) "Efficiency of the flotation method in the isolation of Penicillium marneffei from seeded soil." J Med Vet Mycol 33(4): 271-273 Varga, J (2003) "Mating type gene homologues in Aspergillus fumigatus." 185 Microbiology 149(Pt 4): 816-819 Viviani, M A., A M Tortorano, G Rizzardini, T Quirino, L Kaufman, A A Padhye and L Ajello (1993) "Treatment and serological studies of an Italian case of penicilliosis marneffei contracted in Thailand by a drug addict infected with the human immunodeficiency virus." Eur J Epidemiol 9(1): 79-85 Volling, K., A A Brakhage and H P Saluz (2007) "Apoptosis inhibition of alveolar macrophages upon interaction with conidia of Aspergillus fumigatus." FEMS Microbiol Lett 275(2): 250-254 von Heijne, G (1986) "A new method for predicting signal sequence cleavage sites." Nucleic Acids Res 14(11): 4683-4690 Wald, A., W Leisenring, J A van Burik and R A Bowden (1997) "Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation." J Infect Dis 175(6): 1459-1466 Walsh, T J and D M Dixon (1989) "Nosocomial aspergillosis: environmental microbiology, hospital epidemiology, diagnosis and treatment." Eur J Epidemiol 5(2): 131-142 Wang, F., J Tao, Z Qian, S You, H Dong, H Shen, X Chen, S Tang and S Ren (2009) "A histidine kinase PmHHK1 regulates polar growth, sporulation and cell wall composition in the dimorphic fungus Penicillium marneffei." Mycol Res 113(Pt 9): 915-923 Wang, J E., A Warris, E A Ellingsen, P F Jorgensen, T H Flo, T Espevik, R Solberg, P E Verweij and A O Aasen (2001) "Involvement of CD14 and toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae." Infect Immun 69(4): 2402-2406 Wang, T K., K Y Yuen and S S Wong (2007) "Asymptomatic Penicillium marneffei fungemia in an HIV-infected patient." Int J Infect Dis 11(3): 280-281 Wang, Y and A Casadevall (1994a) "Decreased susceptibility of melanized Cryptococcus neoformans to UV light." Appl Environ Microbiol 60(10): 3864-3866 Wang, Y and A Casadevall (1994b) "Growth of Cryptococcus neoformans in presence of L-dopa decreases its susceptibility to amphotericin B." Antimicrob Agents Chemother 38(11): 2648-2650 Waring, P (1990) "DNA fragmentation induced in macrophages by gliotoxin does not require protein synthesis and is preceded by raised inositol triphosphate levels." J Biol Chem 265(24): 14476-14480 Waring, P., T Khan and A Sjaarda (1997) "Apoptosis induced by gliotoxin is preceded by phosphorylation of histone H3 and enhanced sensitivity of chromatin to nuclease digestion." J Biol Chem 272(29): 17929-17936 Warris, A., A Bjorneklett and P Gaustad (2001) "Invasive pulmonary aspergillosis associated with infliximab therapy." N Engl J Med 344(14): 1099-1100 Warris, A., M G Netea, P E Verweij, P Gaustad, B J Kullberg, C M Weemaes and T G Abrahamsen (2005) "Cytokine responses and regulation of interferon-gamma release by human mononuclear cells to Aspergillus fumigatus and other filamentous fungi." Med Mycol 43(7): 613-621 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(9): 2088-2092 Wasylnka, J A., A H Hissen, A N Wan and M M Moore (2005) "Intracellular and extracellular growth of Aspergillus fumigatus." Med Mycol 43 Suppl 1: 186 S27-30 Weems, J J., Jr., B J Davis, O C Tablan, L Kaufman and W J Martone (1987) "Construction activity: an independent risk factor for invasive aspergillosis and zygomycosis in patients with hematologic malignancy." Infect Control 8(2): 71-75 Wilkins, M R., E Gasteiger, A Bairoch, J C Sanchez, K L Williams, R D Appel and D F Hochstrasser (1999) "Protein identification and analysis tools in the ExPASy server." Methods Mol Biol 112: 531-552 Wong, K H., S S Lee, K C Chan and T Choi (1998) "Redefining AIDS: case exemplified by Penicillium marneffei infection in HIV-infected people in Hong Kong." Int J STD AIDS 9(9): 555-556 Wong, L P., P C Woo, A Y Wu and K Y Yuen (2002) "DNA immunization using a secreted cell wall antigen Mp1p is protective against Penicillium marneffei infection." Vaccine 20(23-24): 2878-2886 Wong, S S., K H Wong, W T Hui, S S Lee, J Y Lo, L Cao and K Y Yuen (2001) "Differences in clinical and laboratory diagnostic characteristics of penicilliosis marneffei in human immunodeficiency virus (HIV)- and non-HIV-infected patients." J Clin Microbiol 39(12): 4535-4540 Woo, P C., C M Chan, A S Leung, S K Lau, X Y Che, S S Wong, L Cao and K Y Yuen (2002) "Detection of cell wall galactomannoprotein Afmp1p in culture supernatants of Aspergillus fumigatus and in sera of aspergillosis patients." J Clin Microbiol 40(11): 4382-4387 Woo, P C., K T Chong, C C Lau, S S Wong, S K Lau and K Y Yuen (2006a) "A novel approach for screening immunogenic proteins in Penicillium marneffei using the DeltaAFMP1DeltaAFMP2 deletion mutant of Aspergillus fumigatus." FEMS Microbiol Lett 262(2): 138-147 Woo, P C., K T Chong, A S Leung, S S Wong, S K Lau and K Y Yuen (2003) "AFLMP1 encodes an antigenic cel wall protein in Aspergillus flavus." J Clin Microbiol 41(2): 845-850 Woo, P C., K T Chong, H Tse, J J Cai, C C Lau, A C Zhou, S K Lau and K Y Yuen (2006b) "Genomic and experimental evidence for a potential sexual cycle in the pathogenic thermal dimorphic fungus Penicillium marneffei." FEBS Lett 580(14): 3409-3416 Woo, P C., C C Lau, K T Chong, H Tse, D N Tsang, R A Lee, C W Tse, T L Que, L M Chung, A H Ngan, W T Hui, S S Wong, S K Lau and K Y Yuen (2007) "MP1 homologue-based multilocus sequence system for typing the pathogenic fungus Penicillium marneffei: a novel approach using lineage-specific genes." J Clin Microbiol 45(11): 3647-3654 Woo, P C., S K Lau, C C Lau, K T Chong, W T Hui, S S Wong and K Y Yuen (2005) "Penicillium marneffei fungaemia in an allogeneic bone marrow transplant recipient." Bone Marrow Transplant 35(8): 831-833 Woo, P C., E W Tam, K T Chong, J J Cai, E T Tung, A H Ngan, S K Lau and K Y Yuen (2010) "High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei." FEBS J 277(18): 3750-3758 Woo, P C., E T Tung, K H Chan, C C Lau, S K Lau and K Y Yuen (2010) "Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies." J Infect Dis 201(3): 346-353 Woo, P C., H Zhen, J J Cai, J Yu, S K Lau, J Wang, J L Teng, S S Wong, R H Tse, R Chen, H Yang, B Liu and K Y Yuen (2003) "The mitochondrial 187 genome of the thermal dimorphic fungus Penicillium marneffei is more closely related to those of molds than yeasts." FEBS Lett 555(3): 469-477 Wu, T C., J W Chan, C K Ng, D N Tsang, M P Lee and P C Li (2008) "Clinical presentations and outcomes of Penicillium marneffei infections: a series from 1994 to 2004." Hong Kong Med J 14(2): 103-109 Yamada, A., T Kataoka and K Nagai (2000) "The fungal metabolite gliotoxin: immunosuppressive activity on CTL-mediated cytotoxicity." Immunol Lett 71(1): 27-32 Yoshida, L S., S Abe and S Tsunawaki (2000) "Fungal gliotoxin targets the onset of superoxide-generating NADPH oxidase of human neutrophils." Biochem Biophys Res Commun 268(3): 716-723 Yuen, K Y., C M Chan, K M Chan, P C Woo, X Y Che, A S Leung and L Cao (2001) "Characterization of AFMP1: a novel target for serodiagnosis of aspergillosis." J Clin Microbiol 39(11): 3830-3837 Yuen, K Y., P C Woo, M S Ip, R H Liang, E K Chiu, H Siau, P L Ho, F F Chen and T K Chan (1997) "Stage-specific manifestation of mold infections in bone marrow transplant recipients: risk factors and clinical significance of positive concentrated smears." Clin Infect Dis 25(1): 37-42 Zhang, Z., H Correa and R E Begue (2002) "Tuberculosis and treatment with infliximab." N Engl J Med 346(8): 623-626 Zhao, W., J C Panepinto, J R Fortwendel, L Fox, B G Oliver, D S Askew and J C Rhodes (2006) "Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence." Infect Immun 74(8): 4865-4874 188 ... Mp1p and Afmp4p, which confer survival advantages to P marneffei and A fumigatus respectively (497 words) Characterization of a novel virulence factor in Penicillium marneffei and Aspergillus fumigatus. .. marneffei or A fumigatus It was shown using a human peripheral blood mononuclear cells model that Mp1p and Afmp4p confer intracellular survival advantage to P marneffei and A fumigatus upon infection... two novel AFMPs namely AFMP3 and AFMP4 Sequence analysis of Afmp3p and Afmp4p revealed the presence of putative N-terminal signal peptide and substantial sequence identity to Mp1p, Afmp1p and Afmp2p