Insights into the interaction of Scedosporium apiospermum, Scedosporium aurantiacum, Scedosporium minutisporum, and Lomentospora prolificans with lung epithelial cells

Abstract

Scedosporium spp. and Lomentospora prolificans are filamentous fungi that emerged as human pathogens; however, their mechanisms of virulence/pathogenesis are still largely unknown. In the present work, we have evaluated the interaction of S. apiospermum, S. minutisporum, S. aurantiacum, and L. prolificans with lung epithelial cells (A549 line). The results showed that conidia were able to interact with A549 cells, displaying association indexes of 73.20, 117.98, 188.01, and 241.63 regarding S. apiospermum, L. prolificans, S. minutisporum, and S. aurantiacum, respectively. Light microscopy images evidenced morphological changes in epithelial cells, including rounding and detachment, especially during the interaction with L. prolificans. Plasma membrane injuries were detected in A549 cells after 1 h of co-culturing with S. aurantiacum and S. minutisporum and after 4 h with S. apiospermum and L. prolificans, as judged by the passive incorporation of propidium iodide. After 24 h of fungi-epithelial cells interaction, only mycelia were observed covering the A549 monolayer. Interestingly, the mycelial trap induced severe damage in the A549 cells, culminating in epithelial cell death. Our results demonstrate some relevant events that occur during the contact between lung epithelial cells and Scedosporium/ Lomentospora species, including conidial adhesion and hyphal growth with consequent irreversible injury on A549 cells, adding light to the infection process caused by these opportunistic and multidrug-resistant fungi.

Fatal pulmonary Scedosporium aurantiacum infection in a patient after near-drowning: A case report

“…In our case, early ARDS was due to contaminated water aspiration and interaction between S. aurantiacum conidia with lung epithelial cells in the early stages of lung injury leading to fungal germination and epithelial cell death. Subsequently, angioinvasion and dissemination of fungi to different parts of the body may take place [ 15 ].…”

Extracellular Vesicles from Scedosporium apiospermum Mycelial Cells: Implication for Fungal-Host Interplays

“…Infections caused by Scedosporium species start with inhalation or inoculation of conidia, which adheres and germinates in the lung tissue; so, the interaction between fungalmammalian cells is a crucial event for scedosporiosis development [67]. In vitro and in vivo data demonstrate that Scedosporium cells are able to interact with different mammalian cell lineages, such as larynx carcinoma cells (HEp2), lung fibroblasts (MRC-5), lung epithelial cells (A549), macrophages (RAW 264.7) and among others [36,[68][69][70][71][72][73]. In general, the interaction event starts with the adhesion of conidia to host cells, with posterior fungal internalization; processes that are partly mediated by the peptideopolysaccharide peptidorhamnomannan (PRM) present in the fungal cell wall [36,69].…”

“…In general, the interaction event starts with the adhesion of conidia to host cells, with posterior fungal internalization; processes that are partly mediated by the peptideopolysaccharide peptidorhamnomannan (PRM) present in the fungal cell wall [36,69]. After a few hours (4 h), conidia adhered to or within the host cell germinate and caused irreversible damage by piercing the mammalian cell membrane [36,70,72]. Another study investigated the exper-iments on the interaction between L. prolificans and microglial cells (BV-2 microglial cell line), demonstrating that phagocytosis by these cells is inefficient against this fungus but is efficient with other fungal species, which are related pathogens, such as Scedosporium boydii and S. aurantiacum.…”

Coccidioidomycosis and Host Microbiome Interactions: What We Know and What We Can Infer from Other Respiratory Infections

“…However, other non-specific inflammatory cytokines may also be released, initiating inflammation and inducing epithelial damage. For instance, in vitro interactions between multiple fungi and epithelial cells reveal morphological changes in epithelial cells such as rounding and detachment, along with cell injury of the epithelial cell plasma membrane [34]. Thus, epithelial damage may be negative for the host but positive for opportunistic invaders and pathogens.…”