Coated Bacteria: Advanced Living Materials for Microbial Therapy

ConspectusLiving materials represent an emerging and innovative concept at the forefronts of materials science due to the distinctive living characteristics. Living organisms, such as microorganisms, plant cells, and mammalian cells, have been used as the major elements for the fabrication of living materials. Given the favorable features including reproductivity, genetic modifiability, adaptability, and cultivability, bacteria have received increasing attention for the development of engineered living materials. Particularly, owing to the inherent abilities to target and colonize specific in vivo sites, activate immune responses, and inhibit pathogens, bacteria play key roles in maintaining human health and have currently widely exploited as living materials for the preparation of therapeutic agents. However, caused by the innate immunogenicity, metabolic activity, and movability, the use of bacteria-based living materials for therapeutic applications often suffers from poor biosafety and insufficient bioavailability, inevitably resulting in low treatment efficacy. In order to address these challenges, extensive efforts have been invested in designing and engineering various advanced bacteria-based living materials to generate superior therapeutic agents by using genetic modification and surface decoration.In this Account, we summarize the recent advances from our group with a focus on surface coating of bacteria-based living material for advanced microbial therapy. First, we present a brief introduction of the existing living materials in nature that possess the living characteristics of reproduction, biosynthesis, self-healing, self-organization, self-adaption, and environment responsiveness, with a particular emphasis on the advantages of living materials composed by bacteria for microbial therapy. Second, we elaborate the current challenges of using bacteria-based living materials for therapeutic applications and then showcase the strategies to prepare superior living bacterial therapeutics by surface coating of individual bacteria. Three types of coating strategies are included in this Account: (1) the physical strategy to coat bacteria with eukaryotic cell membranes from red blood cells and yeast cells by mechanical extrusion; (2) the chemical strategy to wrap bacteria with synthetic coatings by interfacial self-assembly and interfacial mineralization; (3) the biological strategy to encapsulate bacteria by self-secreted biofilms and apoptosis bodies through external stimulations. We highlight that coated bacteria can be endowed with a wide range of coating-derived exogenous functions and enumerate their appealing characteristics of reduced immune clearance, increased bioavailability, improved safety, and preferential colonization in vivo. Third, we shift to the potential of these coated bacteria as living therapeutic agents for treating various diseases, especially different types of cancer and intestinal inflammations. Lastly, we discuss the remaining challenges that need to be addressed for further clinic practice and the outlooks of the engineered bacteria-based living materials by surface coating for preparing next-generation living therapeutic agents as well as their future bench to bedside translation. We anticipate that this Account can offer valuable insights on the generation of bacteria-based living materials and the applications in microbial therapy and encourage innovative ideas and new initiatives to expand the development of advanced living materials for preventing and treating diseases.