Electrochemical DNA Biosensors for Detecting Nontuberculous Mycobacteria

Abstract

Mycobacterial infection and mortality rates remain very high; it is estimated that 10 million cases of Mycobacterium Tuberculosis (M.Tb) emerge each year. However, a less‐studied class of mycobacteria is becoming a growing concern: Nontuberculous Mycobacteria (NTM). Over the last 30 years, NTM‐based lung disease has grown to outnumber M.Tb infections in many regions. The gold standard for positive identification of NTM in a patient sample involves a lengthy microbiological culture‐based method which frequently takes weeks to months in order to make a diagnosis. In this work, we propose a novel electrochemical biosensor that can be used to detect NTM using a DNA aptamer. Our biosensor changes conformational shape when binding to the molecular target mannosylated lipoarabinomannan (ManLAM). ManLAM is a complex lipoglycan abundantly present in the cell envelope of many NTM and M.Tb. This conformational change is measured by voltammetric analysis, and we observe a significant difference in electrochemical current upon binding of ManLAM. We are also expanding our NTM detection efforts through the design of a biosensor targeting glycopeptidolipids (GPL). This strategy will increase our specificity, as GPL is absent from M.Tb. The expected outcome of this project is to greatly improve patient outcomes for NTM infection by allowing rapid, point‐of‐care diagnostics that eliminate invasive sampling and lengthy culturing requirements. This would significantly reduce the time between correct diagnosis and subsequent treatment.