Transcriptomic Insights into the Oxidative Response of Stress-Exposed Aspergillus fumigatus

NADPH-oxidase mediated production of Reactive Oxygen Species (ROS) by alveolar macrophages and neutrophils is a critical mechanism for immune defence against Aspergillus fumigatus. Fungal oxidative stress response includes enzymatic response by superoxide dismutases (SOD), catalases, and enzymes from the thioredoxin and glutathione systems, which are regulated by the transcription factor Yap1. Secondary metabolites are also involved in defense against ROS. Some of the secondary metabolite clusters are controlled by the transcriptional regulator LaeA.

The redundancy of antioxidant systems, and the variable impact of SOD or catalase gene deletions on in vitro oxidative stress sensitivity and in vivo virulence suggest a complex regulation of oxidative stress response in A. fumigatus, making high-throughput approaches, such as microarray or next generation sequencing (NGS), highly relevant to study their respective role. These approaches have been widely applied to A fumigatus, in order to characterize its metabolic response to different stresses mimicking in vivo conditions (such as antifungals, or neutrophils), or to transcription factor deletion (including LaeA). In some studies, oxidative stress response process and antioxidant enzymes have been identified as key metabolic pathways. However, oxidative stress response has not been analyzed systematically and a further data analysis could be helpful to clarify the role of A. fumigatus antioxidant systems and, potentially, to identify new drug targets.

In this review, we synthesized available A. fumigatus microarrays and NGS data, focusing on the role of antioxidant systems. We analyzed the different methodologies that were used for transcriptomic analysis, and we compared biological processes and antioxidant system modulations in A. fumigatus exposed to stress.