Pathogenic Mechanisms of Aspergillus lentulus Infection: Induction of Oxidative Stress and Tissue Damage in Galleria mellonella Larvae.

Abstract

Background: Aspergillus lentulus (A. lentulus) is an emerging pathogenic fungus with intrinsic resistance to multiple antifungal agents. Understanding its pathogenic mechanisms and the host's responses is essential for the development of effective therapeutic strategies. The Galleria mellonella (G. mellonella) larvae model offers a convenient and physiologically relevant in vivo system to investigate fungal virulence and host-pathogen interactions, including the dynamics of oxidative stress.

Methods: In this study, G. mellonella larvae were infected with A. lentulus to assess its virulence. Larval survival rates and intestinal histopathology were evaluated post-infection. Oxidative stress responses were characterized by quantifying intracellular reactive oxygen species (ROS) levels and measuring the activity of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). Additionally, malondialdehyde (MDA) levels were measured as an indicator of lipid peroxidation.

Results: At 24h post-infection, A. lentulus significantly reduced larval survival and caused notable intestinal tissue damage, although its virulence was lower compared to Aspergillus fumigatus (A. fumigatus). The infection induced a marked increase in oxidative stress, as indicated by elevated ROS levels (p < 0.01), reduced activities of the antioxidant enzymes SOD, CAT, and GST, and a 57% increase in MDA content, a marker of lipid peroxidation.

Conclusions: These findings emphasize the role of oxidative stress in host tissue damage during A. lentulus infection. The dual role of ROS in both antimicrobial defense and tissue injury highlights the complexity of host-pathogen interactions. This underscores the potential of targeting oxidative stress pathways as a therapeutic strategy in fungal infections.