Aspergillus fumigatusbiofilms in the clinical setting

Abstract

We discuss in this work the role of Aspergillus biofilms in the clinical setting by reviewing the most recent findings on this topic. Aspergillus fumigatus can produce in vitro an extracellular hydrophobic matrix with typical biofilm characteristics under all static conditions tested, i.e., agar media, polystyrene and bronchial epithelial cells. Under static conditions the mycelial growth is greater than in shaken, submerged conditions. The extracellular matrix (ECM) is composed of galactomannan, α-1,3-glucans, monosaccharides and polyols, melanin and proteins including major antigens and hydrophobins. Typical biofilm structures were observed in the aspergillomas from two patients and in a murine model of invasive pulmonary aspergillosis. The results indicate that α-1,3-glucans plays a predominant role in the agglutination of the hyphae together in aerial conditions, and that nutrient starvation was responsible for mycelial death in aspergilloma. Melanin was produced during the infection, suggesting that this pigment is necessary for lung tissue invasion. All antifungal drugs are significantly less effective when A. fumigatus is grown under biofilm vs. planktonic conditions. Chronic persistence of a unique genotype of A. fumigatus in the respiratory tract of CF-patients and the presence of an ECM in vivo may have some therapeutical application for aspergillosis. The most appropriate antifungal drug should not be selected only on the basis of its efficiency to kill in vitro grown fungal cells, but also on its ability to penetrate the ECM.

Monoclonal Antibodies to Hyphal Exoantigens Derived from the Opportunistic Pathogen Aspergillus terreus

“…Similar structures containing extracellular DNA have been reported in vitro and in vivo and have been identified as the extracellular matrix of fungi (1,37,42). ECMs have only been recently identified, and there is little information on their role in the pathogenesis of fungal infections.…”

In Vitro Interaction between Alginate Lyase and Amphotericin B against Aspergillus fumigatus Biofilm Determined by Different Methods

“…This growth phenotype, which complies with the definition of a biofilm (10), may help A. fumigatus to colonize the host substratum and to resist phagocytic and antimicrobial attacks, mimicking the typical Candida albicans or bacterial biofilm (8,11). Recent observations have consistently shown that all antifungal drugs are significantly less effective when A. fumigatus is grown as a biofilm than when it is grown in the planktonic state (4,7,9,12,13), presumably as a reflection of multiple resistance mechanisms, including the ECM, which would prevent drug diffusion by acting as a physical barrier (14). This could contribute to the overall mortality with invasive aspergillosis, which remains high, despite the use of newer broad-spectrum antifungal agents and diagnostic adjuncts (15).…”

“…S imilar to biofilm-forming bacteria or yeasts (1), Aspergillus fumigatus, the most prevalent airborne fungal pathogen (2), is now largely acknowledged to be an organism able to grow and develop as a multicellular community (3), in which the hyphae are cohesively bonded together by a hydrophobic extracellular matrix (ECM) (4), under the aerial and static conditions found by the fungus either in vitro or in vivo (5)(6)(7)(8)(9). This growth phenotype, which complies with the definition of a biofilm (10), may help A. fumigatus to colonize the host substratum and to resist phagocytic and antimicrobial attacks, mimicking the typical Candida albicans or bacterial biofilm (8,11).…”

Infections associées aux biofilms

“…Bien que des centaines de conidies soient inhalées chaque jour, les cas de pathologies sont rares car le système immunitaire de l'hôte est capable d'éliminer le champignon. Néanmoins, en cas d'altération du système immunitaire ou d'existence de pathologie pulmonaire sous-jacente (séquelle de tuberculose par exemple), il peut être responsable de pathologies graves, certaines pouvant potentiellement être mortelles [67]. Des données récentes montrent qu'A.…”