Selective bioelectronic sensing of quinone pharmaceuticals using extracellular electron transfer in Lactiplantibacillus plantarum

Redox-active small molecules containing quinone functional groups play important roles as pharmaceuticals, but can be toxic if overdosed. Despite the need for a fast and quantitative method to detect quinone and its derivatives, current sensing strategies are often slow and struggle to differentiate between structural analogs. Leveraging the discovery that microorganisms use certain quinones to perform extracellular electron transfer (EET), we investigated the use of Lactiplantibacillus plantarum as a whole-cell bioelectronic sensor to selectively sense quinone analogs. By tailoring the native EET pathway in L. plantarum, we enabled quantitative quinone sensing of 1,4-dihydroxy-2-naphthoic acid (DHNA) - a gut bifidogenic growth stimulator. We found that L. plantarum could respond to environmental DHNA within seconds, producing electronic signals that cover a 106 concentration range. This sensing capacity was robust in different assay media and allowed for continuous monitoring of DHNA concentrations. In a simulated gut environment containing a mixed pool of quinone derivatives, this tailored EET pathway can selectively sense pharmacologically relevant quinone analogs, such as DHNA and menadione, amongst other structurally similar quinone derivatives. We also developed a multivariate model to describe the mechanism behind this selectivity and found a predictable correlation between quinone physiochemical properties and the corresponding electronic signals. Our work presents a new strategy to selectively sense redox-active molecules using whole-cell bioelectronic sensors and opens the possibility of using probiotic L. plantarum for bioelectronic applications in human health. Significant StatementQuinone-containing pharmaceuticals show toxicity at high concentrations, making it important to quickly and accurately measure their concentration while distinguishing between analogs. To address this problem, we leveraged recent discoveries in electroactive bacteria to develop a novel concept for whole-cell sensing. This concept combines selectivity and specificity, enabling differentiation between analogs based on the temporal dynamic of electron transfer in living cells. With this strategy, we achieved selective detection of pharmacologically relevant quinones with distinct electronic signals for each analog. These signals were deciphered by a multivariate model to provide insight into the specific physiochemical properties of each analog. We envision that this new concept can be applied to other analytes for faster and more efficient sensing using electroactive whole cells.