Bacteroidetes and Firmicutes dominate the human gut microbiome, with Bacteroides being the most prevalent genus, highlighting its potential as a therapeutic platform.

Recent studies have shown that Bacteroides species can be genetically engineered for the in situ delivery of therapeutic compounds, offering new strategies to manage chronic diseases such as cancer and diabetes.

This research aims to create a versatile toolkit for developing engineered living therapeutics from Bacteroides species, which could lead to innovative treatments and diagnostics for gastrointestinal diseases.

Engineered living therapeutics employ microbial cell-based strategies to treat diseases from within the human body, leveraging advancements in synthetic biology and our understanding of host-microbiota interactions.

One of the challenges in engineering Bacteroides is their Gram-negative nature, which complicates the efficient secretion of proteins due to their double-membrane structure.

The article investigates various secretion systems in Bacteroides theta, focusing on enhancing the extracellular delivery of heterologous proteins.

Researchers have developed a platform for the secretion of functional proteins, including therapeutic antibodies and reporter proteins, using effective secretion carriers identified from Bacteroides theta.

High-level protein secretion in B. theta was achieved through the use of specific native protein signal sequences, particularly lipoprotein signal peptides, which demonstrated high efficiency in exporting proteins to the extracellular space.

A systematic investigation of secretion carriers revealed that a positively charged region and a length-restricted hydrophobic region are critical for effective protein secretion via lipoprotein signal peptides.