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Crosslinking agents, such as psoralen and UVA radiation, can be effectively used as antimicrobials and for treating several dysplastic conditions in humans, including some cancers. Yet, both cancer cells and bacteria can become resistant to these compounds, making it important to understand how resistance develops. Recently, several mutants were isolated that developed high levels of resistance to these compounds through upregulation of components of the AcrAB-TolC efflux pump. Here, we characterized these mutants and found that resistance specifically requires inactivating mutations of the acrR transcriptional repressor which also retain the marbox sequence found within this coding region. In addition, the presence of any one of three global regulators, MarA, SoxS, or Rob, is necessary and sufficient to bind to the marbox sequence and activate resistance. Notably, although psoralen is a substrate for the efflux pump, these regulators are not naturally responsive to this stress as neither psoralen, UVA, nor crosslink induction upregulates acrAB expression in the absence of mutation. 

DNA has shown great biocompatibility, programmable mechanical properties, and precise structural addressabil- ity at the nanometer scale, rendering it a material for constructing versatile nanorobots for biomedical applica- tions. Here, we present the design principle, synthesis, and characterization of a DNA nanorobotic hand, called DNA NanoGripper, that contains a palm and four bendable fingers as inspired by naturally evolved human hands, bird claws, and bacteriophages. Each NanoGripper finger consists of three phalanges connected by three rotat- able joints that are bendable in response to the binding of other entities. NanoGripper functions are enabled and driven by the interactions between moieties attached to the fingers and their binding partners. We demonstrate that the NanoGripper can be engineered to effectively interact with and capture nanometer-scale objects, includ- ing gold nanoparticles, gold NanoUrchins, and SARS-CoV-2 virions. With multiple DNA aptamer nanoswitches programmed to generate a fluorescent signal that is enhanced on a photonic crystal platform, the NanoGripper functions as a highly sensitive biosensor that selectively detects intact SARS-CoV-2 virions in human saliva with a limit of detection of ~100 copies per milliliter, providing a sensitivity equal to that of reverse transcription quanti- tative polymerase chain reaction (RT-qPCR). Quantified by flow cytometry assays, we demonstrated that the NanoGripper-aptamer complex can effectively block viral entry into the host cells, suggesting its potential for in- hibiting virus infections. The design, synthesis, and characterization of a sophisticated nanomachine that can be tailored for specific applications highlight a promising pathway toward feasible and efficient solutions to the de- tection and potential inhibition of virus infections.