Development and application of novel antibacterial adhesion monoclonal antibodies

Development and application of novel antibacterial adhesion monoclonal antibodies

Bacterial drug resistance has become a global public health problem, and the development of new antibacterial strategies is an important means to solve bacterial resistance. Bacterial colonization and infection typically begin through adhesion to host cells or tissues, a process mediated by adhesins, a class of "adherent" bacterial surface proteins. Since compounds that block this process by antagonizing adhesins do not directly kill bacteria or inhibit their growth, anti-adhesion strategies can greatly mitigate the increase in antibiotic resistance and can therefore be an effective way to defend against bacterial invasion of the host.

Protein glycosylation on the surface of bacteria is thought to be closely related to its adhesion and virulence. The team of Academician Shao Feng of the Beijing Institute of Biological Sciences found that the autologous transporter AIDA-I (adhesin involved in diffusive adhesion) from diffuse Escherichia coli (DAEC) 2787 and TibA from enterotoxic Escherichia coli (ETEC) H10407 were modified by the autologous transporter heptotransferase (AAH) and its ETEC homolog TibC in their passenger domains (Figure 1a) (Cell Host Microbe). 2014）。 In addition, serine heptylation is also essential for bacterial colonization in mice. Thus, this unique serine heptylation modification (Ser-O-Hep) can serve as a potential target against bacterial adhesion to host cells.

Figure 1: Schematic diagram of serine heptylation (Se-O-Hep) and antibody development process. Image credit: J Am Chem Soc

Recently, the team of Professor Hu Honggang of Shanghai University, the team of Professor Zhang Weidong of the Naval Medical University and the team of Professor Lu Wuyuan of Fudan University successfully developed configuration-specific polyclonal and monoclonal antibodies against Ser-O-Hep structure for the first time, and explored the potential of such antibodies for the treatment of bacterial infections. The team synthesized a Ser-O-Hep-modified polypeptide for the first time, successfully screening as a hapten to obtain a highly stereoselective specific recognition antibody in vitro and in vivo (Figure 1b). With the assistance of the team of Academician Shao Feng of the Beijing Institute of Life Sciences, it was further confirmed that these antibodies can effectively recognize various proteins containing Ser-O-Hep. More importantly, Ser-O-Hep monoclonal antibody can effectively prevent the adhesion of DAEC 2787 strain in host cells in vitro and in vivo anti-sensory activity, which is expected to become a new therapeutic strategy for bacterial infection (Figure 2).

Figure 2. Schematic diagram of the antibacterial adhesion effect of Ser-O-Hep-specific monoclonal antibody

The first authors of this research were Li Xiang, associate professor of the Naval Medical University, and Liao Chongbing, a postdoctoral fellow at Fudan University, were recently published in the Journal of the American Chemical Society. Professor Hu Honggang of Shanghai University, Professor Zhang Weidong of Naval Medical University and Professor Lu Wuyuan of Fudan University are co-corresponding authors. The research was also supported by the National Natural Science Foundation of China (21807112, 82030062, 22077078), the National Key Research and Development Program of China (2021YFC2100201) and the Shanghai Science and Technology Daystar Program.