title: Reprogrammable microbial cell-based therapeutics against antibiotic-resistant bacteria.
abstract: The discovery of antimicrobial drugs and their subsequent use has offered an effective treatment option for bacterial infections, reducing morbidity and mortality over the past 60 years. However, the indiscriminate use of antimicrobials in the clinical, community and agricultural settings has resulted in selection for multidrug-resistant bacteria, which has led to the prediction of possible re-entrance to the pre-antibiotic era. The situation is further exacerbated by significantly reduced antimicrobial drug discovery efforts by large pharmaceutical companies, resulting in a steady decline in the number of new antimicrobial agents brought to the market in the past several decades. Consequently, there is a pressing need for new antimicrobial therapies that can be readily designed and implemented. Recently, it has become clear that the administration of broad-spectrum antibiotics can lead to collateral damage to the human commensal microbiota, which plays several key roles in host health. Advances in genetic engineering have opened the possibility of reprogramming commensal bacteria that are in symbiotic existence throughout the human body to implement antimicrobial drugs with high versatility and efficacy against pathogenic bacteria. In this review, we discuss recent advances and potentialities of engineered bacteria in providing a novel antimicrobial strategy against antibiotic resistance.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, 8 Medical Drive, Singapore 117596, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: In Young
authors.initials: IY
authors.lastname: Hwang
authors.affiliation: NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Elvin
authors.initials: E
authors.lastname: Koh
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, 8 Medical Drive, Singapore 117596, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, 8 Medical Drive, Singapore 117596, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
authors.forename: Wen Shan
authors.initials: WS
authors.lastname: Yew
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, 8 Medical Drive, Singapore 117596, Singapore; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), Life Sciences Institute, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore. Electronic address: matthew_chang@nuhs.edu.sg.
authors.forename: Matthew Wook
authors.initials: MW
authors.lastname: Chang
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D001424:Bacterial Infections / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism; D060846:Cell Engineering / Q000379:methods*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D064806:Dysbiosis / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D000069467:Fecal Microbiota Transplantation; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides
keywords: Antibiotic-resistant pathogen; Bacteriocin; Microbiota; Prophylactic agent; Synthetic biology