Biofilms are organized communities of surface-associated microorganisms embedded in a polymeric extracellular matrix. They are common microbial growth forms in nature and during human infection. Emerging evidence suggests that pathogenic fungi produce biofilms during infection, where they play a crucial role in mediating adherence to both host tissues and biomedical devices and provide protection from host immune defenses and antifungal therapy. Biofilm formation by pathogenic microorganisms is considered to be one of the reasons for the drug resistance of pathogens and the difficulty of chronic infectious diseases treatment. However, the underlying molecular regulatory mechanisms of bioflim formation in pathogenic fungi are not fully understood.
Researchers from the School of Life Science of Nanjing Normal University have made an important progress on the regulatory mechanisms of biofilm formation of Aspergillus fumigatus. The article, entitled “The Transcription Factor SomA Synchronously Regulates Biofilm Formation and Cell Wall Homeostasis in Aspergillus fumigatus”, was published in the journal of “mBio” (http://mbio.asm.org/content/11/6/e02329-20.long). Professor Lu Ling and Zhang Shizhu are co-corresponding authors of this paper, Yuan Chen, a doctoral student, is the first author of this paper.
In this study, we found that antifungal agent caspofungin and other cell wall stressors could promote production of the exopolysaccharide galactosaminogalactan (GAG)-depend biofilm formation in the major fungal pathogen of humans Aspergillus fumigatus and that the transcription factor SomA plays a crucial role in mediating this process. Moreover, we identified a novel SomA-binding site in the promoter regions of GAG biosynthetic genes agd3 and ega3, as well as its regulators medA and stuA. Strikingly, this SomA-binding site was also found in the upstream regions of genes encoding the cell wall stress sensors, chitin synthases, and -1,3-glucan synthase. Thus, we identified SomA as a master transcription factor playing a dual role in both biofilm formation and cell wall homeostasis. Collectively, our work provides insight into fungal adaptive mechanisms in response to cell wall stress and sheds light on a regulatory circuit that couples biofilm formation and cell wall homeostasis, and suggest SomA as an attractive target for antifungal drug development.
This study was financially supported by the National Key R&D Program of China and the National Natural Science Foundation of China , the Program for Jiangsu Excellent Scientific and Technological Innovation team.
Working model showing how transcription factor SomA synchronously regulates biofilm formation and cell wall homeostasis