Saravanan Periasamy1, Hwang‐Soo Joo2,3, Anthony C. Duong2,3, Thanh‐Huy L. Bach2,3, Vee Y. Tan2,3, Som S. Chatterjee2,3, Gordon Y. C. Cheung2,3, Michaël Otto2,3
1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
3New York University School of Medicine, New York, NY
Tóm tắt
Biofilms cause significant problems in the environment and during the treatment of infections. However, the molecular mechanisms underlying biofilm formation are poorly understood. There is a particular lack of knowledge about biofilm maturation processes, such as biofilm structuring and detachment, which are deemed crucial for the maintenance of biofilm viability and the dissemination of cells from a biofilm. Here, we identify the phenol-soluble modulin (PSM) surfactant peptides as key biofilm structuring factors in the premier biofilm-forming pathogen
Staphylococcus aureus
. We provide evidence that all known PSM classes participate in structuring and detachment processes. Specifically, absence of PSMs in isogenic
S. aureus psm
deletion mutants led to strongly impaired formation of biofilm channels, abolishment of the characteristic waves of biofilm detachment and regrowth, and loss of control of biofilm expansion. In contrast, induced expression of
psm
loci in preformed biofilms promoted those processes. Furthermore, PSMs facilitated dissemination from an infected catheter in a mouse model of biofilm-associated infection. Moreover, formation of the biofilm structure was linked to strongly variable, quorum sensing-controlled PSM expression in biofilm microenvironments, whereas overall PSM production remained constant to ascertain biofilm homeostasis. Our study describes a mechanism of biofilm structuring in molecular detail, and the general principle (i.e., quorum-sensing controlled expression of surfactants) seems to be conserved in several bacteria, despite the divergence of the respective biofilm-structuring surfactants. These findings provide a deeper understanding of biofilm development processes, which represents an important basis for strategies to interfere with biofilm formation in the environment and human disease.
