Bacteria have been extensively utilized as living therapeutics for disease treatment due to their unique characteristics, such as genetic manipulability, rapid proliferation and specificity to target disease sites. Various in vivo insults can, however, decrease the vitality of dosed bacteria, leading to low overall bioavailability. Additionally, the innate antigens on the bacterial surface and the released toxins and metabolites may cause undesired safety issues. These limitations inevitably result in inadequate treatment outcomes, thereby hindering the clinical transformation of living bacterial therapeutics. Recently, we have developed a versatile platform to prepare advanced living bacterial therapeutics by nanocoating bacteria individually via either chemical decoration or physical encapsulation, which can improve bioavailability and reduce side effects for enhanced microbial therapy. Here we use interfacial self-assembly to prepare lipid membrane-coated bacteria (LCB), exhibiting increased resistance against a variety of harsh environmental conditions owing to the nanocoating's protective capability. Meanwhile, we apply mechanical extrusion to generate cell membrane-coated bacteria (CMCB), displaying improved biocompatibility owing to the nanocoating's shielding effect. We describe their detailed preparation procedures and demonstrate the expected functions of the coated bacteria. We also show that following oral delivery and intravenous injection in mouse models, LCB and CMCB present appealing potential for treating colitis and tumors, respectively. Compared with bioengineering that lacks versatile molecular tools for heterogeneous expression, the surface nanocoating technique is convenient to introduce functional components without restriction on bacterial strain types. Excluding bacterial culture, the fabrication of LCB takes ~2 h, while the preparation of CMCB takes ~5 h.
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The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. Here, RNA sequencing designed to investigate gene expression patterns following CD47-SIRPα inhibition identifies a link between statins, efferocytosis, and vascular inflammation. In vivo and in vitro studies provide evidence that statins augment programmed cell removal by inhibiting the nuclear translocation of NFκB1 p50 and suppressing the expression of the critical 'don't eat me' molecule, CD47. Statins amplify the phagocytic capacity of macrophages, and thus the anti-atherosclerotic effects of CD47-SIRPα blockade, in an additive manner. Analyses of clinical biobank specimens suggest a similar link between statins and CD47 expression in humans, highlighting the potential translational implications. Taken together, our findings identify efferocytosis and CD47 as pivotal mediators of statin pleiotropy. In turn, statins amplify the anti-atherosclerotic effects of pro-phagocytic therapies independently of any lipid-lowering effect.

Bacteria have been extensively utilized for bioimaging, diagnosis and therapy given their unique characteristics including genetic manipulation, rapid proliferation and disease site targeting specificity. However, clinical translation of bacteria for these applications has been largely restricted by their unavoidable side effects and low treatment efficacies. Engineered bacteria for biomedical applications ideally need to generate only a low inflammatory response, show slow elimination by macrophages, low accumulation in normal organs, and almost unchanged inherent bioactivities. Here we describe a set of stealth bacteria, cell membrane coated bacteria (CMCB), meeting these requirement. Our findings are supported by evaluation in multiple mice models and ultimately demonstrate the potential of CMCB to serve as efficient tumor imaging agents. Stealth bacteria wrapped up with cell membranes have the potential for a myriad of bacterial-mediated biomedical applications.