Biofilm formation by<b><i>Aspergillus fumigatus</i></b>

Kaur, Savneet; Singh, Shweta

doi:10.3109/13693786.2013.819592

Cited by 99 publications

(109 citation statements)

References 57 publications

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“…Because of the potential importance of biofilms of A. fumigatus during infection (6,30), particularly in airways, we have examined how iron depletion via a chelator affects biofilm formation and development in vitro. We show that iron chelators have differential effects on the establishment and further development of A. fumigatus biofilms, a finding that is consistent with previous reports of A. fumigatus growing planktonically (10,11).…”

Section: Discussionmentioning

confidence: 99%

Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm

Nazik

Penner

Ferreira

et al. 2015

Antimicrob Agents Chemother

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e Iron acquisition is crucial for the growth of Aspergillus fumigatus. A. fumigatus biofilm formation occurs in vitro and in vivo and is associated with physiological changes. In this study, we assessed the effects of Fe chelators on biofilm formation and development. Deferiprone (DFP), deferasirox (DFS), and deferoxamine (DFM) were tested for MIC against a reference isolate via a broth macrodilution method. The metabolic effects (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt]) on biofilm formation by conidia were studied upon exposure to DFP, DFM, DFP plus FeCl 3 , or FeCl 3 alone. A preformed biofilm was exposed to DFP with or without FeCl 3 . The DFP and DFS MIC 50 against planktonic A. fumigatus was 1,250 M, and XTT gave the same result. DFM showed no planktonic inhibition at concentrations of <2,500 M. By XTT testing, DFM concentrations of <1,250 M had no effect, whereas 2,500 M increased biofilms forming in A. fumigatus or preformed biofilms (P < 0.01). DFP at 156 to 2,500 M inhibited biofilm formation (P < 0.01 to 0.001) in a dose-responsive manner. Biofilm formation with 625 M DFP plus any concentration of FeCl 3 was lower than that in the controls (P < 0.05 to 0.001). FeCl 3 at >625 M reversed the DFP inhibitory effect (P < 0.05 to 0.01), but the reversal was incomplete compared to the controls (P < 0.05 to 0.01). For preformed biofilms, DFP in the range of >625 to 1,250 M was inhibitory compared to the controls (P < 0.01 to 0.001). FeCl 3 at >625 M overcame inhibition by 625 M DFP (P < 0.001). FeCl 3 alone at >156 M stimulated biofilm formation (P < 0.05 to 0.001). Preformed A. fumigatus biofilm increased with 2,500 M FeCl 3 only (P < 0.05). In a strain survey, various susceptibilities of biofilms of A. fumigatus clinical isolates to DFP were noted. In conclusion, iron stimulates biofilm formation and preformed biofilms. Chelators can inhibit or enhance biofilms. Chelation may be a potential therapy for A. fumigatus, but we show here that chelators must be chosen carefully. Individual isolate susceptibility assessments may be needed.A spergillus fumigatus, the ubiquitous saprophytic mold, frequently causes respiratory tract infections, including invasive pulmonary aspergillosis and allergic bronchopulmonary aspergillosis (1). A. fumigatus disease occurs most frequently in immunocompromised individuals, such as bone marrow transplant and other neutropenic patients, solid organ transplant recipients (2), and in those with cystic fibrosis (1, 3), chronic granulomatous disease, or chronic obstructive pulmonary disease (1, 4). Despite therapeutic advances in the development and administration of antifungals, mortality from A. fumigatus infection remains high (5).A. fumigatus has shown, in vivo and in vitro, the ability to form biofilms, or complex aggregates of organisms embedded within a polymer-rich extracellular matrix, which demonstrate increased antimicrobial resistance (32). Thus, there is a need for other therapeutic methods with mechanisms that d...

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Section: Discussionmentioning

confidence: 99%

Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm

Nazik

Penner

Ferreira

et al. 2015

Antimicrob Agents Chemother

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“…Both organisms also contribute to mucus plug formation in the airways and are known to form biofilms (Costerton et al, 1999;Kaur & Singh, 2014). These aggregates of microbes have polymeric matrices that promote adhesion and protect against both antibiotics and host immunity (Hall-Stoodley & Stoodley, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Pseudomonas aeruginosa (Pa) (Govan & Deretic, 1996;Høiby et al, 2010) and Aspergillus fumigatus (Af) (Amin et al, 2010;Baxter et al, 2013;Kaur & Singh, 2014) are the most common bacterium and fungus infecting airways in CF, respectively. Both organisms are associated with a more rapid decline in CF pulmonary function (Fillaux et al, 2012;Nicolai et al, 1990;Ramsey et al, 2014;Schønheyder et al, 1985;Shoseyov et al, 2006;Speirs et al, 2012) and can cause invasive disease (Cahill et al, 1997;Nunley et al, 1998;Yeldandi et al, 1995) or other complications (Botha et al, 2008;Garantziotis & Palmer, 2009;Stevens et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pf4 bacteriophage produced by Pseudomonas aeruginosa inhibits Aspergillus fumigatus metabolism via iron sequestration

et al. 2016

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Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) are major human pathogens known to interact in a variety of disease settings, including airway infections in cystic fibrosis. We recently reported that clinical CF isolates of Pa inhibit the formation and growth of Af biofilms. Here, we report that the bacteriophage Pf4, produced by Pa, can inhibit the metabolic activity of Af biofilms. This phage-mediated inhibition was dose dependent, ablated by phage denaturation, and was more pronounced against preformed Af biofilm rather than biofilm formation. In contrast, planktonic conidial growth was unaffected. Two other phages, Pf1 and fd, did not inhibit Af, nor did supernatant from a Pa strain incapable of producing Pf4. Pf4, but not Pf1, attaches to Af hyphae in an avid and prolonged manner, suggesting that Pf4-mediated inhibition of Af may occur at the biofilm surface. We show that Pf4 binds iron, thus denying Af a crucial resource. Consistent with this, the inhibition of Af metabolism by Pf4 could be overcome with supplemental ferric iron, with preformed biofilm more resistant to reversal. To our knowledge, this is the first report of a bacterium producing a phage that inhibits the growth of a fungus and the first description of a phage behaving as an iron chelator in a biological system. †Present address:

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“…The putative parts list for the A. fumigatus ECM includes polysaccharides (galactomannon, galactosaminogalactan, ␣-1,3 glucans, and monosaccharides), proteins (major antigens and hydrophobins), melanin, and extracellular DNA (8). These identifications relied primarily upon immunoassays, yet suggested compositions vary depending upon the growth conditions and analysis methods.…”

mentioning

confidence: 99%

“…Like many microorganisms, A. fumigatus can also assemble into multicellular communities, termed biofilms, composed of cells plus an extracellular matrix (ECM) (4)(5)(6)(7)(8)(9). Although more work is needed to fully understand the functional implications of biofilm formation by A. fumigatus, recent evidence suggests that the ECM may provide the infrastructure for enhancing cell density, controlling disaggregation, and altering nutritional needs, as well as providing a protective physical and chemical barrier that can decrease sensitivity to competitors and to antifungal drugs and the immune response (10).…”

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confidence: 99%

Analysis of the Aspergillus fumigatus Biofilm Extracellular Matrix by Solid-State Nuclear Magnetic Resonance Spectroscopy

et al. 2015

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dAspergillus fumigatus is commonly responsible for lethal fungal infections among immunosuppressed individuals. A. fumigatus forms biofilm communities that are of increasing biomedical interest due to the association of biofilms with chronic infections and their increased resistance to antifungal agents and host immune factors. Understanding the composition of microbial biofilms and the extracellular matrix is important to understanding function and, ultimately, to developing strategies to inhibit biofilm formation. We implemented a solid-state nuclear magnetic resonance (NMR) approach to define compositional parameters of the A. fumigatus extracellular matrix (ECM) when biofilms are formed in RPMI 1640 nutrient medium. Whole biofilm and isolated matrix networks were also characterized by electron microscopy, and matrix proteins were identified through protein gel analysis. The 13 C NMR results defined and quantified the carbon contributions in the insoluble ECM, including carbonyls, aromatic carbons, polysaccharide carbons (anomeric and nonanomerics), aliphatics, etc. Additional 15 N and 31 P NMR spectra permitted more specific annotation of the carbon pools according to C-N and C-P couplings. Together these data show that the A. fumigatus ECM produced under these growth conditions contains approximately 40% protein, 43% polysaccharide, 3% aromatic-containing components, and up to 14% lipid. These fundamental chemical parameters are needed to consider the relationships between composition and function in the A. fumigatus ECM and will enable future comparisons with other organisms and with A. fumigatus grown under alternate conditions. A spergillus fumigatus is the most important etiological agent of human aspergillosis and is recognized as a highly allergenic and opportunistic pathogen, causing acute and chronic infections particularly among immunocompromised individuals (1). Hospital-associated outbreaks of A. fumigatus may occur during periods of construction or renovation (2) or when fungi colonize water distribution systems that then lead to spore aerosolization in patient care areas and patient exposure (1). Additionally, A. fumigatus can cause infections as a result of colonizing medical implant devices, including cardiac pacemakers, joint replacements, and breast implants (3). Despite improvements in diagnostics and the antifungal armamentarium, including broad-spectrum azoles and the echinocandin antifungals, mortality due to A. fumigatus invasive infections remains high.Like many microorganisms, A. fumigatus can also assemble into multicellular communities, termed biofilms, composed of cells plus an extracellular matrix (ECM) (4-9). Although more work is needed to fully understand the functional implications of biofilm formation by A. fumigatus, recent evidence suggests that the ECM may provide the infrastructure for enhancing cell density, controlling disaggregation, and altering nutritional needs, as well as providing a protective physical and chemical barrier that can decrease sensitivity to competi...

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Biofilm formation byAspergillus fumigatus

Cited by 99 publications

References 57 publications

Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm

Effects of Iron Chelators on the Formation and Development of Aspergillus fumigatus Biofilm

Pf4 bacteriophage produced by Pseudomonas aeruginosa inhibits Aspergillus fumigatus metabolism via iron sequestration

Analysis of the Aspergillus fumigatus Biofilm Extracellular Matrix by Solid-State Nuclear Magnetic Resonance Spectroscopy

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