Research has discovered a new barrier on the mucosal surface

For many pathogens, the initial point of entry into the host is mucosal epithelial cells, and the host's immune system deploys several defense mechanisms on this surface, including the mucus itself. Now, Barr et al. Pointed out that bacteriophage may constitute an additional antibacterial defense mechanism on the mucosal surface of the host.

Based on these findings, Barr et al. Proposed a model in which soluble bacteriophages bind to the polysaccharide component of mucin through the Ig-like domain on the surface of the protein, thereby using bacteria to form an antibacterial layer that can reduce mucus colonization and thus protect the underlying Raw skin cells are protected from infection. They further proposed that the hypermutation of the Ig-like domain and the dynamic properties of mucus—not only changing in structure but also continuously decaying on the outer surface—will enable the bacteriophage to quickly adapt to changes in mucus and bacterial invasion.

The authors sampled the mucosal surfaces of a range of organisms and found that the ratio of bacteriophages to bacteria on these surfaces is approximately four times that of the former compared to the surrounding environment. Examination of bacteriophage T4 adhered to human cell lines showed that more phage adhered to mucus-producing cells than cells that did not produce mucus, and chemical removal of mucus reduced the phage's Adhere.

Many bacteriophages in the human intestinal tract use hypervariable immunoglobulin (Ig) -like domains—associated with cell adhesion in many organisms—to encode proteins. The T4 surface protein Hoc (having a highly antigenic outer capsid) contains four such domains, and the authors speculate that they may bind to the components of mucus. In fact, compared to a mutant lacking Hoc, the increase in the number of T4 phage adhering to mucin-coated agar relative to the non-agar-coated T4 phage is very large for wild-type phage . In addition, the authors found that although wild-type T4 can bind different mammalian polysaccharides, it has a special affinity for these polysaccharides commonly found in mucin glycoproteins, and Hoc-deficient phages were tested on all 610 polysaccharides Has shown limited binding ability. Therefore, the bacteriophage T4 seems to be able to adhere to mucus through the interaction of Hoc with mucin polysaccharide.

Soluble phages, such as T4, kill strains that compete with their host strains. To test whether such dissolution activities can reduce bacterial colonization on the mucosal surface, the authors evaluated the effects of E. coli exposed to mucosa-producing tissue culture cells that had been pretreated with bacteriophage T4. Compared with cells that were not pretreated, bacterial adhesion and skin cell death were significantly reduced in T4 pretreated cells, meaning that the phage had a protective effect on the skin cells.

The relevance of this model in the intestinal environment and its applicability to mild bacteriophages (common in the intestine) remain to be seen, and the potential for therapeutic development, such as phage-modulated immunity, still needs to be explored. This discovery will undoubtedly become a springboard for many key discoveries in the future.

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