1887

Abstract

The fungal pathogen is frequently cultured from the sputum of cystic fibrosis (CF) patients along with the bacterium secretes a range of secondary metabolites, and one of these, gliotoxin, has inhibitory effects on the host immune response. The effect of culture filtrate (CuF) on fungal growth and gliotoxin production was investigated. Exposure of hyphae to cells induced increased production of gliotoxin and a decrease in fungal growth. In contrast, exposure of hyphae to CuF led to increased growth and decreased gliotoxin production. Quantitative proteomic analysis was used to characterize the proteomic response of upon exposure to CuF. Changes in the profile of proteins involved in secondary metabolite biosynthesis (e.g. gliotoxin, fumagillin, pseurotin A), and changes to the abundance of proteins involved in oxidative stress (e.g. formate dehydrogenase) and detoxification (e.g. thioredoxin reductase) were observed, indicating that the bacterial secretome had a profound effect on the fungal proteome. Alterations in the abundance of proteins involved in detoxification and oxidative stress highlight the ability of to differentially regulate protein synthesis in response to environmental stresses imposed by competitors such as . Such responses may ultimately have serious detrimental effects on the host.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.001164
2022-03-25
2022-05-18
Loading full text...

Full text loading...

/deliver/fulltext/micro/168/3/mic001164.html?itemId=/content/journal/micro/10.1099/mic.0.001164&mimeType=html&fmt=ahah

References

  1. Vivek-Ananth RP, Mohanraj K, Vandanashree M, Jhingran A, Craig JP et al. Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species. Sci Rep 2018; 8:6617 [View Article] [PubMed]
    [Google Scholar]
  2. Wartenberg D, Lapp K, Jacobsen ID, Dahse H-M, Kniemeyer O et al. Secretome analysis of Aspergillus fumigatus reveals Asp-hemolysin as a major secreted protein. Int J Med Microbiol 2011; 301:602–611 [View Article] [PubMed]
    [Google Scholar]
  3. Behnsen J, Lessing F, Schindler S, Wartenberg D, Jacobsen ID et al. Secreted Aspergillus fumigatus protease Alp1 degrades human complement proteins C3, C4, and C5. Infect Immun 2010; 78:3585–3594 [View Article] [PubMed]
    [Google Scholar]
  4. Wang D, Zhang L, Zou H, Wang L. Secretome profiling reveals temperature-dependent growth of Aspergillus fumigatus . Sci China Life Sci 2018; 61:578–592 [View Article] [PubMed]
    [Google Scholar]
  5. Tekaia F, Latgé J-P. Aspergillus fumigatus: saprophyte or pathogen?. Curr Opin Microbiol 2005; 8:385–392 [View Article] [PubMed]
    [Google Scholar]
  6. Paulussen C, Hallsworth JE, Álvarez-Pérez S, Nierman WC, Hamill PG et al. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol 2017; 10:296–322 [View Article] [PubMed]
    [Google Scholar]
  7. Bignell E, Cairns TC, Throckmorton K, Nierman WC, Keller NP. Secondary metabolite arsenal of an opportunistic pathogenic fungus. Phil Trans R Soc B 2016; 371:20160023 [View Article] [PubMed]
    [Google Scholar]
  8. Inglis DO, Binkley J, Skrzypek MS, Arnaud MB, Cerqueira GC et al. Comprehensive annotation of secondary metabolite biosynthetic genes and gene clusters of Aspergillus nidulans, A. fumigatus, A. niger and A. oryzae . BMC Microbiol 2013; 13:91 [View Article] [PubMed]
    [Google Scholar]
  9. Raffa N, Keller NP, Sheppard DC. A call to arms: Mustering secondary metabolites for success and survival of an opportunistic pathogen. PLOS Pathog 2019; 15:e1007606 [View Article] [PubMed]
    [Google Scholar]
  10. Amin S, Thywissen A, Heinekamp T, Saluz HP, Brakhage AA. Melanin dependent survival of Apergillus fumigatus conidia in lung epithelial cells. Int J Med Microbiol 2014; 304:626–636 [View Article] [PubMed]
    [Google Scholar]
  11. Fallon JP, Reeves EP, Kavanagh K. Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin fumagillin. J Med Microbiol 2010; 59:625–633 [View Article] [PubMed]
    [Google Scholar]
  12. Schlam D, Canton J, Carreño M, Kopinski H, Freeman SA et al. Gliotoxin suppresses macrophage immune function by subverting phosphatidylinositol 3,4,5-trisphosphate homeostasis. mBio 2016; 7:1–15 [View Article]
    [Google Scholar]
  13. Coburn B, Wang PW, Diaz Caballero J, Clark ST, Brahma V et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 2015; 5:10241 [View Article] [PubMed]
    [Google Scholar]
  14. Breuer O, Schultz A, Garratt LW, Turkovic L, Rosenow T et al. Aspergillus infections and progression of structural lung disease in children with cystic fibrosis. Am J Respir Crit Care Med 2020; 201:688–696 [View Article] [PubMed]
    [Google Scholar]
  15. Reece E, McClean S, Greally P, Renwick J. The prevalence of Aspergillus fumigatus in early cystic fibrosis disease is underestimated by culture-based diagnostic methods. J Microbiol Methods 2019; 164:105683 [View Article] [PubMed]
    [Google Scholar]
  16. Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis 2003; 37 Suppl 3:S225–64 [View Article] [PubMed]
    [Google Scholar]
  17. Maturu VN, Agarwal R. Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and meta-analysis. Clin Exp Allergy 2015; 45:1765–1778 [View Article] [PubMed]
    [Google Scholar]
  18. Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol 2013; 51:361–370 [View Article] [PubMed]
    [Google Scholar]
  19. Armstead J, Morris J, Denning DW. Multi-country estimate of different manifestations of aspergillosis in cystic fibrosis. PLOS ONE 2014; 9:e98502 [View Article] [PubMed]
    [Google Scholar]
  20. Reece E, Segurado R, Jackson A, McClean S, Renwick J et al. Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis. BMC Pulm Med 2017; 17:1–8 [View Article] [PubMed]
    [Google Scholar]
  21. Zhao J, Cheng W, He X, Liu Y. The co-colonization prevalence of Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis: A systematic review and meta-analysis. Microb Pathog 2018; 125:122–128 [View Article] [PubMed]
    [Google Scholar]
  22. Fothergill JL, Walshaw MJ, Winstanley C. Transmissible strains of Pseudomonas aeruginosa in cystic fibrosis lung infections. Eur Respir J 2012; 40:227–238 [View Article]
    [Google Scholar]
  23. Hector A, Kirn T, Ralhan A, Graepler-Mainka U, Berenbrinker S et al. Microbial colonization and lung function in adolescents with cystic fibrosis. J Cyst Fibros 2016; 15:340–349 [View Article] [PubMed]
    [Google Scholar]
  24. Reece E, Segurado R, Jackson A, McClean S, Renwick J et al. Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis. BMC Pulm Med 2017; 17:70 [View Article] [PubMed]
    [Google Scholar]
  25. Zhao J, Cheng W, He X, Liu Y. The co-colonization prevalence of Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis: A systematic review and meta-analysis. Microb Pathog 2018; 125:122–128 [View Article] [PubMed]
    [Google Scholar]
  26. Paugam A, Baixench M-T, Demazes-Dufeu N, Burgel P-R, Sauter E et al. Characteristics and consequences of airway colonization by filamentous fungi in 201 adult patients with cystic fibrosis in France. Med Mycol 2010; 48 Suppl 1:S32–6 [View Article] [PubMed]
    [Google Scholar]
  27. Yonezawa M, Sugiyama H, Kizawa K, Hori R, Mitsuyama J et al. A new model of pulmonary superinfection with Aspergillus fumigatus and Pseudomonas aeruginosa in mice. J Infect Chemother 2000; 6:155–161 [View Article] [PubMed]
    [Google Scholar]
  28. Briard B, Bomme P, Lechner BE, Mislin GLA, Lair V et al. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Sci Rep 2015; 5:8220 [View Article] [PubMed]
    [Google Scholar]
  29. Sass G, Nazik H, Penner J, Shah H, Ansari SR et al. Studies of Pseudomonas aeruginosa mutants indicate pyoverdine as the central factor in inhibition of Aspergillus fumigatus biofilm. J Bacteriol 2018; 200:1–24 [View Article] [PubMed]
    [Google Scholar]
  30. Shirazi F, Ferreira JAG, Stevens DA, Clemons KV, Kontoyiannis DP. Biofilm filtrates of Pseudomonas aeruginosa strains isolated from cystic fibrosis patients inhibit preformed Aspergillus fumigatus biofilms via apoptosis. PLoS One 2016; 11:e0150155 [View Article] [PubMed]
    [Google Scholar]
  31. Ferreira JAG, Penner JC, Moss RB, Haagensen JAJ, Clemons KV et al. Inhibition of Aspergillus fumigatus and its biofilm by Pseudomonas aeruginosa is dependent on the source, phenotype and growth conditions of the bacterium. PLOS ONE 2015; 10:e0134692 [View Article] [PubMed]
    [Google Scholar]
  32. Mowat E, Rajendran R, Williams C, McCulloch E, Jones B et al. Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation. FEMS Microbiology Letters 2010; 313:96–102 [View Article] [PubMed]
    [Google Scholar]
  33. Reece E, Doyle S, Greally P, Renwick J, McClean S. Aspergillus fumigatus inhibits Pseudomonas aeruginosa in co-culture: implications of a mutually antagonistic relationship on virulence and inflammation in the CF airway. Front Microbiol 2018; 9:1–14 [View Article] [PubMed]
    [Google Scholar]
  34. Margalit A, Carolan JC, Sheehan D, Kavanagh K. The Aspergillus fumigatus secretome alters the proteome of Pseudomonas aeruginosa to stimulate bacterial growth: implications for co-infection. Molecular & Cellular Proteomics 2020; 19:1346–1359 [View Article] [PubMed]
    [Google Scholar]
  35. Briard B, Heddergott C, Latgé J-P, Taylor JW, Dunlap JC et al. Volatile compounds emitted by Pseudomonas aeruginosa stimulate growth of the fungal pathogen Aspergillus fumigatus . mBio 2016; 7:1–5 [View Article] [PubMed]
    [Google Scholar]
  36. Scott J, Sueiro-Olivares M, Ahmed W, Heddergott C, Zhao C et al. Pseudomonas aeruginosa-derived volatile sulfur compounds promote distal Aspergillus fumigatus growth and a synergistic pathogen-pathogen interaction that increases pathogenicity in co-infection. Front Microbiol 2019; 10:2311 [View Article] [PubMed]
    [Google Scholar]
  37. Nazik H, Sass G, Déziel E, Stevens DA. Aspergillus is inhibited by Pseudomonas aeruginosa volatiles. JoF 2020; 6:118 [View Article]
    [Google Scholar]
  38. Smith K, Rajendran R, Kerr S, Lappin DF, Mackay WG et al. Aspergillus fumigatus enhances elastase production in Pseudomonas aeruginosa co-cultures. Med Mycol 2015; 53:645–655 [View Article] [PubMed]
    [Google Scholar]
  39. Sass G, Ansari SR, Dietl A-M, Déziel E, Haas H et al. Intermicrobial interaction: Aspergillus fumigatus siderophores protect against competition by Pseudomonas aeruginosa . PLoS One 2019; 14:e0216085 [View Article] [PubMed]
    [Google Scholar]
  40. Hubner NC, Bird AW, Cox J, Splettstoesser B, Bandilla P et al. Quantitative proteomics combined with BAC TransgeneOmics reveals in vivo protein interactions. J Cell Biol 2010; 189:739–754 [View Article] [PubMed]
    [Google Scholar]
  41. Côté RG, Griss J, Dianes JA, Wang R, Wright JC et al. The PRoteomics IDEntification (PRIDE) converter 2 framework: an improved suite of tools to facilitate data submission to the PRIDE Database and the ProteomeXchange Consortium. Molecular & Cellular Proteomics 2012; 11:1682–1689 [View Article] [PubMed]
    [Google Scholar]
  42. Murphy S, Zweyer M, Mundegar RR, Swandulla D, Ohlendieck K. Proteomic identification of elevated saliva kallikrein levels in the mdx-4cv mouse model of Duchenne muscular dystrophy. Biochem Biophys Rep 2019; 18:100541 [View Article]
    [Google Scholar]
  43. Briard B, Rasoldier V, Bomme P, ElAouad N, Guerreiro C et al. Dirhamnolipids secreted from Pseudomonas aeruginosa modify anjpegungal susceptibility of Aspergillus fumigatus by inhibiting β1,3 glucan synthase activity. ISME J 2017; 11:1578–1591 [View Article] [PubMed]
    [Google Scholar]
  44. Briard B, Mislin GLA, Latgé J-P, Beauvais A. Interactions between Aspergillus fumigatus and pulmonary bacteria: current state of the field, new data, and future perspective. J Fungi (Basel) 2019; 5:48 [View Article] [PubMed]
    [Google Scholar]
  45. Cramer RA, Gamcsik MP, Brooking RM, Najvar LK, Kirkpatrick WR et al. Disruption of a nonribosomal peptide synthetase in Aspergillus fumigatus eliminates gliotoxin production. Eukaryot Cell 2006; 5:972–980 [View Article] [PubMed]
    [Google Scholar]
  46. Dolan SK, Owens RA, O’Keeffe G, Hammel S, Fitzpatrick DA et al. Regulation of nonribosomal peptide synthesis: bis-thiomethylation attenuates gliotoxin biosynthesis in Aspergillus fumigatus . Chem Biol 2014; 21:999–1012 [View Article] [PubMed]
    [Google Scholar]
  47. Line L, Alhede M, Kolpen M, Kühl M, Ciofu O et al. Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum. Front Microbiol 2014; 5:554 [View Article] [PubMed]
    [Google Scholar]
  48. Wurster S, Sass G, Albert ND, Nazik H, Déziel E et al. Live imaging and quantitative analysis of Aspergillus fumigatus growth and morphology during inter-microbial interaction with Pseudomonas aeruginosa . Virulence 2020; 11:1329–1336 [View Article] [PubMed]
    [Google Scholar]
  49. Margalit A, Carolan JC, Kavanagh K. Bacterial Interactions with Aspergillus fumigatus in the Immunocompromised Lung. Microorganisms 2021; 9:435 [View Article] [PubMed]
    [Google Scholar]
  50. Abalos A, Pinazo A, Infante MR, Casals M, García F et al. Physicochemical and antimicrobial properties of new rhamnolipids produced by Pseudomonas a eruginosa AT10 from soybean oil refinery wastes. Langmuir 2001; 17:1367–1371 [View Article]
    [Google Scholar]
  51. Stanzani M, Orciuolo E, Lewis R, Kontoyiannis DP, Martins SLR et al. Aspergillus fumigatus suppresses the human cellular immune response via gliotoxin-mediated apoptosis of monocytes. Blood 2005; 105:2258–2265 [View Article] [PubMed]
    [Google Scholar]
  52. Schlam D, Canton J, Carreño M, Kopinski H, Freeman SA et al. Gliotoxin suppresses macrophage immune function by subverting phosphatidylinositol 3,4,5-trisphosphate homeostasis. mBio 2016; 7:e02242 [View Article] [PubMed]
    [Google Scholar]
  53. Orciuolo E, Stanzani M, Canestraro M, Galimberti S, Carulli G et al. Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis. J Leukoc Biol 2007; 82:839–848 [View Article] [PubMed]
    [Google Scholar]
  54. Reese KL, Rasley A, Avila JR, Jones AD, Frank M. Metabolic Profiling of Volatile Organic Compounds (VOCs) emitted by the pathogens Francisella tularensis and Bacillus anthracis in liquid culture. Sci Rep 2020; 10:9333 [View Article] [PubMed]
    [Google Scholar]
  55. da Cruz Nizer WS, Inkovskiy V, Versey Z, Strempel N, Cassol E et al. Oxidative stress response in Pseudomonas aeruginosa . Pathogens 2021; 10:1187 [View Article] [PubMed]
    [Google Scholar]
  56. Ahn S, Jung J, Jang I-A, Madsen EL, Park W. Role of glyoxylate shunt in oxidative stress response. J Biol Chem 2016; 291:11928–11938 [View Article] [PubMed]
    [Google Scholar]
  57. Meyer KC, Sharma A, Brown R, Weatherly M, Moya FR et al. Function and composition of pulmonary surfactant and surfactant-derived fatty acid profiles are altered in young adults with cystic fibrosis. Chest 2000; 118:164–174 [View Article] [PubMed]
    [Google Scholar]
  58. Son MS, Matthews WJ Jr, Kang Y, Nguyen DT, Hoang TT. In vivo evidence of Pseudomonas aeruginosa nutrient acquisition and pathogenesis in the lungs of cystic fibrosis patients. Infect Immun 2007; 75:5313–5324 [View Article] [PubMed]
    [Google Scholar]
  59. Lund P, Tramonti A, De Biase D. Coping with low pH: molecular strategies in neutralophilic bacteria. FEMS Microbiol Rev 2014; 38:1091–1125 [View Article] [PubMed]
    [Google Scholar]
  60. Ratzke C, Gore J. Modifying and reacting to the environmental pH can drive bacterial interactions. PLoS Biol 2018; 16:e2004248 [View Article] [PubMed]
    [Google Scholar]
  61. Cunin R, Glansdorff N, Piérard A, Stalon V. Biosynthesis and metabolism of arginine in bacteria. Microbiol Rev 1986; 50:314–352 [View Article]
    [Google Scholar]
  62. Brosch G, Loidl P, Graessle S. Histone modifications and chromatin dynamics: a focus on filamentous fungi. FEMS Microbiol Rev 2008; 32:409–439 [View Article] [PubMed]
    [Google Scholar]
  63. Palmer JM, Perrin RM, Dagenais TRT, Keller NP. H3K9 methylation regulates growth and development in Aspergillus fumigatus . Eukaryot Cell 2008; 7:2052–2060 [View Article] [PubMed]
    [Google Scholar]
  64. Bladt TT, Frisvad JC, Knudsen PB, Larsen TO. Anticancer and antifungal compounds from Aspergillus, Penicillium and other filamentous fungi. Molecules 2013; 18:11338–11376 [View Article] [PubMed]
    [Google Scholar]
  65. Martínez-Luis S, Cherigo L, Arnold E, Spadafora C, Gerwick WH et al. Antiparasitic and anticancer constituents of the endophytic fungus Aspergillus sp. strain F1544. Nat Prod Commun 2012; 7:1934578X1200700 [View Article]
    [Google Scholar]
  66. Wenke J, Anke H, Sterner O. Pseurotin A and 8- O -Demethylpseurotin A from Aspergillus fumigatus and their inhibitory activities on chitin synthase. Biosci Biotechnol Biochem 2014; 57:961–964 [View Article]
    [Google Scholar]
  67. Khoufache K, Puel O, Loiseau N, Delaforge M, Rivollet D et al. Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells. BMC Microbiol 2007; 7:5 [View Article] [PubMed]
    [Google Scholar]
  68. Tepšič K, Gunde-Cimerman N, Frisvad JC. Growth and mycotoxin production by Aspergillus fumigatus strains isolated from a saltern. FEMS Microbiology Letters 2006; 157:9–12 [View Article]
    [Google Scholar]
  69. Fallon JP, Reeves EP, Kavanagh K. Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin fumagillin. J Med Microbiol 2010; 59:625–633 [View Article] [PubMed]
    [Google Scholar]
  70. Doyle S, Jones GW, Dolan SK. Dysregulated gliotoxin biosynthesis attenuates the production of unrelated biosynthetic gene cluster-encoded metabolites in Aspergillus fumigatus . Fungal Biol 2018; 122:214–221 [View Article] [PubMed]
    [Google Scholar]
  71. Sugui JA, Kim HS, Zarember KA, Chang YC, Gallin JI et al. Genes differentially expressed in conidia and hyphae of Aspergillus fumigatus upon exposure to human neutrophils. PLOS ONE 2008; 3:e2655 [View Article] [PubMed]
    [Google Scholar]
  72. Marshall AC, Kidd SE, Lamont-Friedrich SJ, Arentz G, Hoffmann P et al. Structure, mechanism, and inhibition of Aspergillus fumigatus thioredoxin reductase. Antimicrob Agents Chemother 2019; 63:e02281-18 [View Article] [PubMed]
    [Google Scholar]
  73. Paris S, Wysong D, Debeaupuis J-P, Shibuya K, Philippe B et al. Catalases of Aspergillus fumigatus . Infect Immun 2003; 71:3551–3562 [View Article] [PubMed]
    [Google Scholar]
  74. Li L, Hu X, Xia Y, Xiao G, Zheng P et al. Linkage of oxidative stress and mitochondrial dysfunctions to spontaneous culture degeneration in Aspergillus nidulans . Mol Cell Proteomics 2014; 13:449–461 [View Article] [PubMed]
    [Google Scholar]
  75. Gayathri L, Akbarsha MA, Ruckmani K. In vitro study on aspects of molecular mechanisms underlying invasive aspergillosis caused by gliotoxin and fumagillin, alone and in combination. Sci Rep 2020; 10:14473 [View Article] [PubMed]
    [Google Scholar]
  76. Islam MT, Mishra SK, Tripathi S, de Alencar MVOB, E Sousa JM de C et al. Mycotoxin-assisted mitochondrial dysfunction and cytotoxicity: Unexploited tools against proliferative disorders. IUBMB Life 2018; 70:1084–1092 [View Article] [PubMed]
    [Google Scholar]
  77. Gallagher L, Owens RA, Dolan SK, O’Keeffe G, Schrettl M et al. The Aspergillus fumigatus protein GliK protects against oxidative stress and is essential for gliotoxin biosynthesis. Eukaryot Cell 2012; 11:1226–1238 [View Article]
    [Google Scholar]
  78. Schrettl M, Carberry S, Kavanagh K, Haas H, Jones GW et al. Self-protection against gliotoxin--a component of the gliotoxin biosynthetic cluster, GliT, completely protects Aspergillus fumigatus against exogenous gliotoxin. PLoS Pathog 2010; 6:e1000952 [View Article] [PubMed]
    [Google Scholar]
  79. Fang FC, Frawley ER, Tapscott T, Vázquez-Torres A. Bacterial stress responses during host infection. Cell Host Microbe 2016; 20:133–143 [View Article] [PubMed]
    [Google Scholar]
  80. Abad A, Fernández-Molina JV, Bikandi J, Ramírez A, Margareto J et al. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol 2010; 27:155–182 [View Article] [PubMed]
    [Google Scholar]
  81. Reichard U, Cole GT, Hill TW, Rüchel R, Monod M. Molecular characterization and influence on fungal development of ALP2, a novel serine proteinase from Aspergillus fumigatus . Int J Med Microbiol 2000; 290:549–558 [View Article] [PubMed]
    [Google Scholar]
  82. Burgel P-R, Paugam A, Hubert D, Martin C. Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy. Infect Drug Resist 2016; 9:229–238 [View Article] [PubMed]
    [Google Scholar]
  83. Dagenais TRT, Keller NP. Pathogenesis of Aspergillus fumigatus in invasive Aspergillosis . Clin Microbiol Rev 2009; 22:447–465 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.001164
Loading
/content/journal/micro/10.1099/mic.0.001164
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 2

EXCEL

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error