title: Biological nanofactories facilitate spatially selective capture and manipulation of quorum sensing bacteria in a bioMEMS device.
abstract: The emergence of bacteria that evade antibiotics has accelerated research on alternative approaches that do not target cell viability. One such approach targets cell-cell communication networks mediated by small molecule signaling. In this report, we assemble biological nanofactories within a bioMEMS device to capture and manipulate the behavior of quorum sensing (QS) bacteria as a step toward modifying small molecule signaling. Biological nanofactories are bio-inspired nanoscale constructs which can include modules with different functionalities, such as cell targeting, molecular sensing, product synthesis, and ultimately self-destruction. The biological nanofactories reported here consist of targeting, sensing, synthesis and, importantly, assembly modules. A bacteria-specific antibody constitutes the targeting module while a genetically engineered fusion protein contains the sensing, synthesis and assembly modules. The nanofactories are assembled on chitosan electrodeposited within a microchannel of the bioMEMS device; they capture QS bacteria in a spatially selective manner and locally synthesize and deliver the "universal" small signaling molecule autoinducer-2 (AI-2) at the captured cell surface. The nanofactory based AI-2 delivery is demonstrated to alter the progression of the native AI-2 based QS response of the captured bacteria. Prospects are envisioned for utilizing our technique as a test-bed for understanding the AI-2 based QS response of bacteria as a means for developing the next generation of antimicrobials.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
authors.forename: Rohan
authors.initials: R
authors.lastname: Fernandes
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Luo
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Tsao
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Payne
authors.forename: Reza
authors.initials: R
authors.lastname: Ghodssi
authors.forename: Gary W
authors.initials: GW
authors.lastname: Rubloff
authors.forename: William E
authors.initials: WE
authors.lastname: Bentley
mesh_terms: D001681:Biological Assay / Q000295:instrumentation; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002469:Cell Separation / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D004926:Escherichia coli / Q000502:physiology*; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D008846:Micromanipulation / Q000295:instrumentation*; D036103:Nanotechnology / Q000295:instrumentation; D053038:Quorum Sensing / Q000502:physiology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity