Peptide Molecular Siege Machine: Breaking through Mycobacterium tuberculosis’s Cellular Defenses for Precise Detection and Monitoring

Abstract

This work introduces a peptide biosensor for detecting Mycobacterium tuberculosis (Mtb). The designed peptide probe exhibits specific affinity toward distinct components of Mtb. First, a peptide sequence is tailored to target hydrophobic long-chain fatty acids in the mycobacterial cell wall. Following this, an electrochemical potential scan releases a peptide sequence aimed at the intracellular molecular chaperones of Mtb. This sequence, upon penetration of the bacterial cell membrane, binds with molecular chaperones, which is crucial for Mtb survival and stress response. The biosensor incorporates complementary peptide sequences to capture chaperone-bound peptides back onto the substrate surface, allowing for their subsequent electrochemical detection. This multistep process enables selective and sequential interactions with Mtb components, minimizing interference from nontarget molecules. By integrating these innovative peptide probes into a wearable substrate using conductive polymer technology, the biosensor achieves high sensitivity and accuracy, offering a promising tool for the real-time monitoring of tuberculosis progression and treatment response.