Aspergillus Biofilm In Vitro and In Vivo

Abstract

In vivo, Aspergillus fumigatus grows as a typical biofilm with hyphae covered by an extracellular matrix (ECM) composed of polysaccharides, galactomannan, and galactosaminogalactan. α1,3 glucans and melanin are also constitutive of the ECM in aspergilloma but not in invasive aspergillosis. In vitro, two biofilm models were established to mimic the in vivo situation. The first model (model 1) uses submerged liquid conditions and is characterized by slow growth, while the second model (model 2) uses agar medium and aerial conditions and is characterized by rapid growth. The composition of the ECM was studied only in the second model and has been shown to be composed of galactomannan, galactosaminogalactan (GAG), and α1,3 glucans, melanin, antigens, and hydrophobins. The presence of extracellular DNA was detected in model 1 biofilm but not in model 2. Transcriptomic analysis employing both biofilm models showed upregulation of genes coding for proteins involved in the biosynthesis of secondary metabolites, adhesion, and drug resistance. However, most data on A. fumigatus biofilms have been obtained in vitro and should be confirmed using in vivo animal models. There is a need for new therapeutic antibiofilm strategies that focus on the use of combination therapy, since biofilm formation poses an important clinical problem due to their resistance to antifungal agents. Furthermore, in vivo investigations of A. fumigatus biofilms that incorporate the associated microbiota are needed. Such studies will add another layer of complexity to our understanding of the role of A. fumigatus biofilm during lung invasion.

Characteristics of Aspergillus fumigatus in Association with Stenotrophomonas maltophilia in an In Vitro Model of Mixed Biofilm

“…[26] as swollen conidia started germination between 4 and 8 h in order to form a monolayer of hyphae, followed by an intense filamentation to create a complex hyphal network at 24 h of culture (Fig 2A). The production of ECM in the fungal biofilm was visible at 12 h and increased until 24 h, the maturation phase, where the fungi was totally covered by the matrix (Fig 2), in consistency with the results of Beauvais and Latgé [18]. The microscopic analyses of this biofilm helped visualise the hyphae in the ECM which formed a resistant structure covering the hyphae and the spaces between them (Fig 2B) [21].…”

“…In vitro , biofilms with single A . fumigatus [18–21] or S . maltophilia [22–24] showed standard growth, yet and to our knowledge, no study on mixed biofilm of these two organisms has been conducted.…”

Biosynthesis of cell wall mannan in the conidium and the mycelium ofAspergillusfumigatus

“…Such structural differences were observed in the chitin microfibrils of the mycelium cell wall of chs mutant, which have either short or long microfibrils while their content in chitin is similar (Muszkieta et al, ). This is also seen in the localization of the α1,3 glucans, which is different in both morphotypes (Beauvais & Latgé, ). These studies indicated that the structural organization of the cell wall polysaccharides and their modifications during morphological changes remain poorly understood.…”

Candida Biofilms: Development, Architecture, and Resistance

“…These studies have provided extensive knowledge of the effect of different variables, including growth time, nutrients, and physiological conditions, on biofilm formation, morphology, and architecture ( 15 ). In this chapter, we will focus on Candida biofilms (biofilms caused by Aspergillus are covered in reference 155 ) and provide an update on their development, architecture, and resistance mechanisms.…”