Chapter 41 : A Perspective on Research for the Next Ten Years

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

A Perspective on Research for the Next Ten Years, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815523/9781555814380_Chap41-1.gif /docserver/preview/fulltext/10.1128/9781555815523/9781555814380_Chap41-2.gif


In patients, invasive aspergillosis remains one of the most difficult diagnoses, and treatment is often late and unsuccessful. This chapter presents some thoughts and unpublished data from laboratories as well as questions that have been repeatedly discussed in meetings which should open new research avenues and may question some ongoing ones. Why is pathogenic to human beings? This question automatically leads to the hypothesis of the presence of virulence factors specifically synthesized by that are essential for invasion of its mammalian host. According to anti-aspergillus therapies, there are currently 11 antifungals with anti-Aspergillus activity, and several others are under evaluation in early clinical and preclinical studies. One of the most debated topics is the issue of combination antifungal therapy against invasive aspergillosis. The number of severely immunocompromised patients will continue to increase over the next 10 years as the field of medicine develops the technology to treat an increasing number of underlying conditions, such as malignancy and failed organs. Similarly, other medical disciplines such as rheumatology and gastroenterology are increasingly starting to use immunosuppressive agents for their recalcitrant patients, further multiplying the number of patients at risk for invasive aspergillosis.

Citation: Latgé J, Steinbach W. 2009. A Perspective on Research for the Next Ten Years, p 549-558. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch41

Key Concept Ranking

Aspergillus fumigatus
Microbial Virulence Factors
Positron Emission Tomography
Magnetic Resonance Imaging
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Germination of conidia of in vitro and in vivo. (A) Binding to and internalization of a conidium by an alveolar macrophage. (B) The first stages of germination (swelling) are not affected in the phagolysosome of the alveolar macrophage. (C) Killing of the conidium in an alveolar macrophage of an immunocompetent mouse. (D) Germination of the conidium in an alveolar macrophage of a cortisone acetate-treated mouse. (E) Three characteristic stages of conidial germination: a resting conidium with a thick melanin outer layer; a swollen conidium characterized by plasticization of the existing cell wall layers and synthesis of a new inner layer; and germling formation with disruption of the outer melanin layer and establishment of a polarized cell surrounded by the neosynthesized cell wall emerging through the outer conidia glucan layer. Adapted from .

Citation: Latgé J, Steinbach W. 2009. A Perspective on Research for the Next Ten Years, p 549-558. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch41
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Percentage of killing of conidia of (gray bars) and (black bars) by alveolar macrophages of immunocompetent (IC) and immunosuppressed (IS) mice recovered from bronchoal-veolar lavage fluid 24 h after conidia inhalation.

Citation: Latgé J, Steinbach W. 2009. A Perspective on Research for the Next Ten Years, p 549-558. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch41
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

strain virulence seen as differential fitness during joint infections. (A) Survival curve of cortisone acetate-treated mice infected intranasally with a unique strain, one of three strains with pigmentless conidia (W1 [ ], W2 [ ], W3 [ ]) or one of three strains with green-pigmented conidia (G1 [♦], G2 [▴], G3 [ ]; solid line, control). (B) Number of strains isolated from lungs of mice infected with the six strains together (hatched bars, intranasally; solid bars, intravenously). Note that strains G1 and G3 are the ones found in larger amounts (the most fit for growth in the lung) and that strain W3 is more pathogenic than the two other white strains and green strain G2. Adapted from Sarfati et al. (2002).

Citation: Latgé J, Steinbach W. 2009. A Perspective on Research for the Next Ten Years, p 549-558. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch41
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4.
Figure 4.

Two diagrams showing the interconnection between partners and disciplines in the study of aspergillosis in laboratory (A) and hospital (B) settings.

Citation: Latgé J, Steinbach W. 2009. A Perspective on Research for the Next Ten Years, p 549-558. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch41
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Anderson, J. B. 2005. Evolution of antifungaldrug resistance: mechanisms and pathogen fitness. Nat. Rev. Microbiol. 3: 547556.
2. Balloy, V.,, M. Huerre,, J. P. Latgé, and, M. Chignard. 2005. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect. Immun. 73:494503.
3. Bellocchio, S.,, S. Bozza,, C. Montagnoli,, K. Perruccio,, R. Gaziano,, L. Pitzurra, and, L. Romani. 2005. Immunity to Aspergillus fumigatus: the basis for immunotherapy and vaccination. Med. Mycol. Suppl. 1:S181S188.
4. Brown, A. J.,, F. C. Odds, and, N. A. Gow. 2007. Infection-related gene expression in Candida albicans. Curr. Opin. Microbiol. 10: 307313.
5. Caillot, D.,, O. Casasnovas,, A. Bernard,, J. F. Couaillier,, C. Durand,, B. Cuisenier,, E. Solary,, F. Piard,, T. Petrella,, A. Bonnin,, G. Couil-lault,, M. Dumas, and, H. Guy. 1997. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J. Clin. Oncol. 15:139147.
6. Carvalho, A.,, A. C. Pasqualotto,, L. Pitzurra,, L. Romani,, D. W. Denning, and, F. Rodrigues. 2008. Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J. Infect. Dis. 197:618621.
7. Cegelski, L.,, G. R. Marshall,, G. R. Eldridge, and, S. J. Hultgren. 2008. The biology and future prospects of antivirulence therapies. Nat. Rev. Microbiol. 6:1727.
8. Chazalet, V.,, J. P. Debeaupuis,, J. Sarfati,, J. Lortholary,, P. Ribaud,, P. Shah,, M. Cornet,, H. Vu Thien,, E. Gluckman,, G. Brücker, and, J. P. Latgé. 1998. Molecular typing of environmental and patient isolates of Aspergillus fumigatus from various hospital settings. J. Clin. Microbiol. 36:14941500.
9. Dadachova, E., and, A. Casadevall. 2008. Host and microbial cells as targets for armed antibodies in the treatment of infectious diseases. Curr. Opin. Investig. Drugs 9:184188.
10. Dadachova, E.,, A. Nakouzi,, R. A. Bryan, and, A. Casadevall. 2003. Ionizing radiation delivered by specific antibody is therapeutic against a fungal infection. Proc. Natl. Acad. Sci. USA 100: 1094210947.
11. de Hoog, G. S.,, J. Guarro,, J. Gené, and, M. J. Figueras. 2005. Atlas of Clinical Fungi, p. 1126. Centraalbureau voor Schimmelcultures, Utrecht, The Netherlands.
12. Henry, C.,, I. Mouyna, and, J. P. Latgé. 2007. Testing the efficacy of RNA interference constructs in Aspergillus fumigatus. Curr. Genet. 51:277284.
13. Herrero, E.,, J. Ros,, G. Belli, and, E. Cabiscol. 2008. Redox control and oxidative stress in yeast cells. Biochim. Biophys. Acta. 1780: 12171235.
14. Ibrahim-Granet, O.,, M. Dubourdeau,, J. P. Latgé,, P. Ave,, M. Huerre,, A. A. Brakhage, and, M. Brock. 2008. Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis. Cell. Microbiol. 10:134148.
15. Jahn, B.,, F. Boukhallouk,, J. Lotz,, K. Langfelder,, G. Wanner, and, A. A. Brakhage. 2000. Interaction of human phagocytes with pigmentless Aspergillus conidia. Infect. Immun. 68:37363739.
16. Johnson, L. B., and, C. A. Kauffman. 2003. Voriconazole: a new triazole antifungal agent. Clin. Infect. Dis. 36:630637.
17. Kniemeyer, O.,, F. Lessing,, O. Scheibner,, C. Hertweck, and, A. A. Brakhage. 2006. Optimisation of a 2-D gel electrophoresis protocol for the humanpathogenic fungus Aspergillus fumigatus. Curr. Genet. 49:178189.
18. Lessing, F.,, O. Kniemeyer,, I. Wozniok,, J. Loeffler,, O. Kurzai,, A. Haertl, and, A. A. Brakhage. 2007. The Aspergillus fumigatus tran-scriptional regulator AfYap1 represents the major regulator for defence against reactive oxygen intermediates but is dispensable for pathogenicity in an intranasal mouse infection model. Eukaryot. Cell 6:22902302.
19. Marr, K. A.,, R. A. Carter,, F. Crippa,, A. Wald, and, L. Corey. 2002. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin. Infect. Dis. 34:909917.
20. Mezger, M.,, M. Steffens,, M. Beyer,, C. Manger,, J. Eberle,, M. R. To-liat,, T. F. Wienker,, P. Ljungman,, H. Hebart,, H. J. Dornbusch,, H. Einsele, and, J. Loeffler. 2008. Polymorphisms in the chemokine (C- X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 expression in monocyte-derived dendritic cells. Blood 111:534536.
21. Montagnoli, C.,, K. Perruccio,, S. Bozza,, P. Bonifazi,, T. Zelante,, A. De Luca,, S. Moretti,, C. D’Angelo,, F. Bistoni,, M. Martelli,, F. Av-ersa,, A. Velardi, and, L. Romani. 2008. Provision of antifungal immunity and concomitant alloantigen tolerization by conditioned dendritic cells in experimental hematopoietic transplantation. Blood Cells Mol. Dis. 40:5562.
22. Moreno, M. A.,, O. Ibrahim-Granet,, R. Vicentefranqueira,, J. Amich,, P. Ave,, F. Leal,, J. P. Latgé, and, J. A. Calera. 2007. The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence. Mol. Microbiol. 64:11821197.
23. Mylonakis, E.,, A. Casadevall, and, F. M. Ausubel. 2007. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi. PLoS Pathog. 3:e101.
24. 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 106:43974406.
25. Philippe, B.,, O. Ibrahim-Granet,, M. C. Prévost,, M. A. Gougerot-Pocidalo,, M. Sanchez Perez,, A. Van der Meeren, and, J. P. Latgé. 2003. Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect. Immun. 71: 30343042.
26. Sarfati, J.,, M. Diaquin,, J. P. Debeaupuis,, A. Schmidt,, D. Lecaque,, A. Beauvais, and, J. P. Latgé. 2002. A new experimental murine aspergillosis model to identify strains of Aspergillus fumigatus with reduced virulence. Nippon Ishinkin Gakkai Zasshi 43:203213.
27. Schrettl, M.,, E. Bignell,, C. Kragl,, Y. Sabiha,, O. Loss,, M. Eisendle,, A. Wallner,, H. N. Arst, Jr.,, K. Haynes, and, H. Haas. 2007. Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLoS Pathog. 3: 11951207.
28. Schroeder, G. N., and, H. Hilbi. 2008. Molecular pathogenesis of Shi-gella spp.: controlling host cell signalling, invasion, and death by type III secretion. Clin. Microbiol. Rev. 21: 134156.
29. Segal, A. W. 2005. How neutrophils kill microbes. Annu. Rev. Immunol. 23:197223.
30. Speth, E. B.,, Y. N. Lee, and, S. Y. He. 2007. Pathogen virulence factors as molecular probes of basic plant cellular functions. Curr. Opin. Plant Biol. 10:580586.
31. 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: 479486.
32. Tekaia, F., and, J. P. Latgé. 2005. Aspergillus fumigatus: saprophyte or pathogen? Curr. Opin. Microbiol. 8: 385392.
33. Temple, M. D.,, G. G. Perrone, and, I. W. Dawes. 2005. Complex cellular responses to reactive oxygen species. Trends Cell Biol. 15: 319326.
34. Torosantucci, A.,, C. Bromuro,, P. Chiani,, F. De Bernardis,, F. Berti,, C. Galli,, F. Norelli,, C. Bellucci,, L. Polonelli,, P. Costantino,, R. Rap-puoli, and, A. Cassone. 2005. A novel glyco-conjugate vaccine against fungal pathogens. J. Exp. Med. 202:597606.
35. van der Does, H. C., and, M. Rep. 2007. Virulence genes and the evolution of host specificity in plant-pathogenic fungi. Mol. Plant Microbe Interact. 20:11751182.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error