Receptor-targeted engineered probiotics mitigate lethal Listeria infection.

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Probiotics can inhibit pathogen colonization, but their efficacy against foodborne Listeria monocytogenes (Lm) is variable.
• Developing strategies to enhance probiotic effectiveness against Lm is crucial for public health.

Purpose of the Study:

• To engineer Lactobacillus probiotics to express Listeria adhesion protein (LAP) for improved Lm exclusion.
• To evaluate the efficacy of bioengineered Lactobacillus probiotics (BLP) in preventing Lm infection in a mouse model.

Main Methods:

• Lactobacillus casei was engineered to express LAP from non-pathogenic and pathogenic Listeria species.
• BLP colonization, Lm colonization, systemic dissemination, and survival rates were assessed in mice.
• Mechanisms including receptor binding, intestinal barrier function, and immune cell recruitment were investigated.

Main Results:

• Engineered BLP successfully colonized the intestine and reduced Lm mucosal colonization and systemic spread.
• BLP protected mice from lethal Lm infection by competitively excluding Lm and ameliorating intestinal barrier dysfunction.
• BLP enhanced intestinal immunity by recruiting regulatory T cells, dendritic cells, and natural killer cells.

Conclusions:

• Engineering probiotics with adhesion proteins offers a novel approach to pathogen exclusion.
• Bioengineered probiotics demonstrate significant potential for preventing fatal foodborne infections and enhancing gut health.