Proximity Ligation Mediated Signal Recycling with Primer Exchange Reaction for Sensitive and Accurate Methicillin-Resistant Staphylococcus Aureus (MRSA) Detection

Abstract Background Infectious diseases have emerged as a significant global concern, posing a substantial burden in terms of the high morbidity and mortality, and presenting considerable challenges in clinical diagnosis and treatment. Therefore, it is highly-desired to develop new strategies for sensitive and accurate bacteria detection to address the global epidemic of antibiotic resistance. Results In this study, a new technique combining proximity ligation and primer exchange reaction (PER) was developed for precise identification and highly sensitive detection of Methicillin-Resistant Staphylococcus Aureus (MRSA). The antibodies recognize both protein A and PBP2a on the surface of MRSA, leading to the initiation of proximity ligation and PER process. The PER procedure generated a substantial number of G-quadruplex sequences, which subsequently bind with thioflavin T (ThT) to significantly amplify its fluorescence, enabling the detection of MRSA with a low detection limit of 3.5 cfu/mL. Conclusion Due to its non-label format, high selectivity, and sensitivity, this method can serve as a practical and versatile approach for detecting different bacteria in the early stages of infectious diseases.