The virulence of Aspergillus fumigatus

Osherov, Nir

doi:10.1007/978-1-4020-6397-8_8

Cited by 9 publications

(8 citation statements)

References 154 publications

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“…fumigatus in vivo , however a double deletion mutant did increase survival [ 49 ]. Despite this, it is difficult to assess the inclusion of catalases as virulence factors due to redundancy; the fungus possesses many genes that aid in combating ROS, including five catalases ( catA , cat1 / catB , catC , catE , and cat2 / katG ) and four superoxide dismutatases: sod1, sod2, sod3, and sod4 [ 49 , 74 , 75 ]. It is possible that although cat1 and cat2 are expressed at higher levels in the mutant strain, rtfA could be required for other factors involved in oxidative stress resistance.…”

Section: Discussionmentioning

confidence: 99%

rtfA controls development, secondary metabolism, and virulence in Aspergillus fumigatus

et al. 2017

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Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection-related mortality in immune-compromised patients. In order to discover potential genetic targets to control A. fumigatus infections we characterized rtfA, a gene encoding a putative RNA polymerase II transcription elongation factor-like protein. Our recent work has shown that the rtfA ortholog in the model fungus Aspergillus nidulans regulates morphogenesis and secondary metabolism. The present study on the opportunistic pathogen A. fumigatus rtfA gene revealed that this gene influences fungal growth and conidiation, as well as production of the secondary metabolites tryptoquivaline F, pseurotin A, fumiquinazoline C, festuclavine, and fumigaclavines A, B and C. Additionally, rtfA influences protease activity levels, the sensitivity to oxidative stress and adhesion capacity, all factors important in pathogenicity. Furthermore, rtfA was shown to be indispensable for normal virulence using Galleria mellonella as well as murine infection model systems.

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Section: Discussionmentioning

confidence: 99%

rtfA controls development, secondary metabolism, and virulence in Aspergillus fumigatus

et al. 2017

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“…Evidence accumulating over the last decade suggests that A. fumigatus utilizes multiple virulence factors to infect and colonize its host, including toxins and proteases, protective pigments and antioxidants, thermotolerance, and small spore size (26).…”

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confidence: 99%

Transcription Factor PrtT Controls Expression of Multiple Secreted Proteases in the Human Pathogenic Mold Aspergillus fumigatus

2009

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The role of secreted proteases in the virulence of the pathogenic fungus Aspergillus fumigatus remains controversial. Recently, the Aspergillus niger transcription factor PrtT was shown to control the expression of multiple secreted proteases. In this work, the gene which encodes the PrtT homolog in A. fumigatus was cloned and its function analyzed using a deletion mutant strain. Deletion of A. fumigatus prtT resulted in the loss of secreted protease activity. The expression of six secreted proteases (ALP, MEP, Dpp4, CpdS, AFUA_2G17330, and AFUA_7G06220) was markedly reduced. Culture filtrates from the prtT deletion strain exhibited reduced killing of lung epithelial cells and lysis of erythrocytes. However, the prtT deletion strain did not exhibit altered virulence in lung-infected mice. These results suggest that PrtT is not a significant virulence factor in A. fumigatus.Fungi belonging to the genus Aspergillus are important opportunistic pathogens of immunocompromised patients. Aspergillus fumigatus is the main causative agent of aspergillosis. In the last 15 years there has been a sharp upsurge in the incidence and severity of fungal infections caused by these organisms. This has been attributed to more aggressive cytotoxic chemotherapy, an increase in the number of bone marrow and organ transplant recipients, and the emergence of AIDS (18).Evidence accumulating over the last decade suggests that A. fumigatus utilizes multiple virulence factors to infect and colonize its host, including toxins and proteases, protective pigments and antioxidants, thermotolerance, and small spore size (26).Proteases have been implicated as virulence factors in viral (9), bacterial (8, 38), and fungal (22, 23a) pathogenesis. The following evidence implicates secreted A. fumigatus proteases in virulence: (i) secreted A. fumigatus proteases induce proinflammatory cytokine release in infected macrophages and epithelial cells, thereby alerting the immune system (14); (ii) infected lung epithelial cells also undergo protease-dependent changes to the actin cytoskeleton, leading to cell peeling and death (15, 36); (iii) proteases are secreted in vivo during infection, and protease-specific antisera show labeling of mycelium in the lungs of patients and experimentally infected animals (22); (iv) loss of elastase protease activity in mutagenized strains of A. fumigatus has been correlated with decreased virulence in vivo (16); and (v) mice intratracheally injected with purified ALP1 protease showed a marked degree of lower respiratory tract destruction (10).However, deletion analyses of selected proteases (ALP1, MEP, PEP1, MEP, and ALP1) have failed to conclusively demonstrate a significant role in virulence in animal models (22). This is probably due to the large number of proteases secreted by A. fumigatus and the functional redundancy among them. Its genome encodes approximately 111 proteases and 26 nonpeptidase homologs (MEROPS peptidase database for A. fumigatus, http://merops.sanger.ac.uk/), of which 47 have a signal sequence dire...

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“…Along with cell surface proteins, the secretome of A. fumigatus represents a focal point of the host:pathogen interface comprising various enzymes, adhesins and toxins [4,57]. The relevance of this in host recognition is exemplified in immunoproteomic analysis indicating the presence of many proteins reactive with IgG and IgE from ABPA, IA and aspergilloma patients [17,[20][21][22].…”

Section: The Secretome and Proteasesmentioning

confidence: 99%

Proteomic analysis of Aspergillus fumigatus – clinical implications

Moloney

Owens

Doyle

2016

Expert Review of Proteomics

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The traits that make A. fumigatus a successful colonizer and pathogen of humans are multi-factorial. Thus, a global investigative approach is required to elucidate the mechanisms utilized by the fungus to cause disease. Expert commentary: In doing so, a better understanding of disease pathology can be achieved with improved therapeutic/diagnostic solutions, thereby improving patient outcome. Proteomic analysis permits such investigations and recent work has yielded insight into these mechanisms.

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The virulence of Aspergillus fumigatus

Cited by 9 publications

References 154 publications

rtfA controls development, secondary metabolism, and virulence in Aspergillus fumigatus

rtfA controls development, secondary metabolism, and virulence in Aspergillus fumigatus

Transcription Factor PrtT Controls Expression of Multiple Secreted Proteases in the Human Pathogenic Mold Aspergillus fumigatus

Proteomic analysis of Aspergillus fumigatus – clinical implications

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