Engineered endolysin-based “artilysins” for controlling the gram-negative pathogen Helicobacter pylori

作者：Dengyuan Xu, Shanshan Zhao, Jun Dou, Xiaofeng Xu, Yanyan Zhi, Liangzhu Wen · 发表于：AMB Express · 年份：2021 · DOI：10.1186/s13568-021-01222-8 · 被引用次数：36 · 研究领域：Bacteriophages and microbial interactions、Monoclonal and Polyclonal Antibodies Research、Viral gastroenteritis research and epidemiology

Helicobacter pylori infection can cause a variety of gastrointestinal diseases. In severe cases, there is a risk of gastric cancer. Antibiotics are often used for clinical treatment of H. pylori infections. However, because of antibiotic overuse in recent years and the emergence of multidrug-resistant bacteria, there is an urgent need to develop new treatment methods and drugs to achieve complete eradication of H. pylori. Endolysins and holins encoded by bacterial viruses (i.e., phages) represent a promising avenue of investigation. These lyase-based antibacterial drugs act on the bacterial cell wall to destroy the bacteria. Currently, a type of endolysin that has been studied more frequently acts on the amide bond between peptidoglycans, and holin is a transmembrane protein that can punch holes in the cell membrane. However, as a Gram-negative bacterium, H. pylori possesses a layer of impermeable lipopolysaccharides on the cell wall, which prevents endolysin interaction with the cell wall. Therefore, we designed a genetic linkage between an endolysin enzyme and a holin enzyme with a section of polypeptides (e.g., polycations and hydrophobic peptides) that enable penetration of the outer membrane. These complexes were designated "artilysins" and were efficiently expressed in Escherichia coli. In vitro bacteriostasis experiments showed that the purified artilysins had strong bacteriostatic effects on H. pylori. In addition, the surface of H. pylori was perforated and destroyed...