Dijun Du, PhDAssistant Professor

Main research areas-I: Molecular mechanisms of antibiotic resistance

Broadly resistant Gram-negative bacteria are a common cause of hospital-acquired infections and deaths. Multidrug resistance in bacteria stems from a variety of molecular mechanisms, including enzymatic degradation of antibiotics, changes in bacterial proteins that serve as antimicrobial targets, changes in membrane permeability, and efflux pumps that actively pump antibiotics out of cells.

Although resistance pumps are one of the main factors leading to broad-spectrum resistance in Gram-negative bacteria, no antimicrobial drugs targeting resistance pumps have been developed. The envelope of Gram-negative bacteria is a strong protective layer, which mainly consists of three layers: an outer cell membrane covered with lipopolysaccharide; an inner cell membrane that directly contacts the intracellular substances; and a periplasm between the inner and outer membranes, in which the cell wall composed of peptidoglycan is located, which provides mechanical rigidity to the cell. Gram-negative bacteria have some special cell membrane protein complexes that transport substrates from the cell through the entire envelope layer to the outside of the cell. The tripartite multidrug efflux pump is one of such nanomolecular machines, which can directly expel antibiotics out of the cell. The tripartite multidrug efflux pump complex contains an outer membrane channel protein and an inner membrane transport protein, as well as a membrane fusion protein located in the periplasm that connects the inner membrane protein and the outer membrane protein to form a complete transport channel.

The inner membrane protein is usually an efflux pump of the RND protein family. This multidrug resistance pump tripartite complex composed of the RND protein family obtains antibiotics from the periplasm and excretes them out of the cell; while drug efflux pumps of the ABC, MFS, SMR, MATE and PACT protein families usually only transport antibiotics from the cell to the periplasm.

One of the main research areas of our research group is the structure and molecular mechanism of pathogen resistance pumps. These studies can guide the development of new antibiotics.

Main Research Areas-II: Molecular Mechanisms of Viral Pathogenesis

Viral pathogenesis involves complex interactions between viruses and hosts, including virus invasion of host cells, replication, transmission, and eventual disease development, which are usually mediated by viral proteins and host immune responses.

The enveloped virus membrane fusion protein is located on the surface of the virus particle and is responsible for mediating the fusion of the viral envelope with the host cell membrane, releasing the viral genetic material into the cell, and completing the infection of the host cell. The membrane fusion protein exists in a metastable pre-fusion form on the surface of the virus particle. This metastable form of protein is essential for its function, enabling the protein to transform into a lower energy post-fusion state through conformational changes, while using the released energy to catalyze the membrane fusion process. Blocking the conformational transition of the pre-fusion state membrane fusion protein can effectively prevent viral invasion. Therefore, the pre-fusion state membrane fusion protein is a key target for the development of preventive vaccines, antibodies, and antiviral drugs.

One of the main research areas of this research group is the structure and molecular mechanism of viral membrane fusion proteins, including Epstein-Barr virus (EBV) and cytomegalovirus (HCMV), etc. EB virus and cytomegalovirus are closely related to the occurrence of many diseases such as nasopharyngeal carcinoma, lymphoma and deafness. Elucidating the structure and molecular mechanism of  virus membrane fusion protein will lay the foundation for the development of vaccines to prevent tumors such as nasopharyngeal carcinoma and lymphoma.