|Meng Guoyu’s team of the affiliated Ruijin Hospitalpublished an article on biofilm formation mechanismon eLife|
On November 10, the world-renownedmagazine eLife published online the latest biofilm research paper entitled “Structural basis ofhost recognition and biofilm formation by Salmonella Saf pili” by Shanghai Jiao Tong University School of Medicine Ruijin Hospital, Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, whichreports the mechanism of Salmonella atypical pilus Saf mediating biofilm formation.
Bacterial biofilm is a kind of aggregated membrane sample which is formed by the bacteriasecretion of a large amount of extracellular matrix such as polysaccharides, proteins and nucleic acids in order to adapt to the environment and to adhere to the surface of the object or human tissue. Biofilms are closely linked to human health, such as the formation of tooth plaque and the implantation of implanted medical devices. Compared to a single planktonic bacterium,the formation of biofilms is more resistant to antibiotics and the host immune system, causing the infection to become chronic and recurrent, leading to serious clinical problems. Therefore, the formation mechanism of biofilm has been the focus of scholars at home and abroad.
Meng Guoyu‘s team has been long committed to blood diseases and pathogenic infections structural biology research. In a biofilm study, the team first proposed in the top issue (The EMBO Journal, 2011) that the pathogenic virulence protein Hap-adhesin mediates intercellular aggregation resulting in the formation of microcolonies and biofilms.
In eLife’s report, the study focused on the “killer” salmonella hidden around us, which was responsible for large-scale food poisoning.The research focused on Saf pili that is specifically expressed on the surface of most clinically-pathogenic Salmonella and consists of a single apical SafD subunit connecting multiple SafA subunits, which has been found to have poly-adhesive activity and self-associating activity. To understand the mechanism of Saf pili, researchers obtained the high-resolution protein structure of a single SafD and three consecutive subunits SafDAA by structural biology. Through analyzing the cell structure of proteinSafDAA, it is bold to propose a hypothesis model that Saf pili mediates biofilm formation by end-to-end “handshake” oligomerization, which was multi-angle confirmed this modelby researchers using biophysical methods (SAXS, SEC-MALS) and cell function experiments. This study, combined with previous findings at EMBO J, demonstrated that it is common for bacteria to promote biofilm formation through oligomerization of intercellular adhesion molecules. The researchers also found that proline (Pro20), a link between the various subunits of the linked pilus, changes its conformation through its specific cis-trans conversion, affecting biofilm formation. It is worth mentioning that proline is highly conserved among other types of pilus subunits linker.
This basic research has potential application value. On the one hand, it provides a fine view of the target protein structure for the prevention and treatment of Salmonella (such as vaccine and antibody development). On the other hand, the elaboration on the formation mechanism of biofilm provides a new idea of inhibiting bacterial oligomerization (not to kill bacteria) for solving the problem of exacerbating global antibiotic resistance in the world.
Meng Guoyu doctoral student Zeng Longhui, Zhang Li and post-doctoral student Wang Pengran were tied for the first author. Professor Mengguoyu is the communication author. The research obtained the support of National Natural Science Foundation of China, Shanghai Science and Technology Commission of Education Committee and Oriental Scholars Fund and Shanghai Synchrotron Radiation Source!