{"doi":"10.1038/s42003-021-01856-1","title":"Facile accelerated specific therapeutic (FAST) platform develops antisense therapies to counter multidrug-resistant bacteria","abstract":"Multidrug-resistant (MDR) bacteria pose a grave concern to global health, which is perpetuated by a lack of new treatments and countermeasure platforms to combat outbreaks or antibiotic resistance. To address this, we have developed a Facile Accelerated Specific Therapeutic (FAST) platform that can develop effective peptide nucleic acid (PNA) therapies against MDR bacteria within a week. Our FAST platform uses a bioinformatics toolbox to design sequence-specific PNAs targeting non-traditional pathways/genes of bacteria, then performs in-situ synthesis, validation, and efficacy testing of selected PNAs. As a proof of concept, these PNAs were tested against five MDR clinical isolates: carbapenem-resistant Escherichia coli, extended-spectrum beta-lactamase Klebsiella pneumoniae, New Delhi Metallo-beta-lactamase-1 carrying Klebsiella pneumoniae, and MDR Salmonella enterica. PNAs showed significant growth inhibition for 82% of treatments, with nearly 18% of treatments leading to greater than 97% decrease. Further, these PNAs are capable of potentiating antibiotic activity in the clinical isolates despite presence of cognate resistance genes. Finally, the FAST platform offers a novel delivery approach to overcome limited transport of PNAs into mammalian cells by repurposing the bacterial Type III secretion system in conjunction with a kill switch that is effective at eliminating 99.6% of an intracellular Salmonella infection in human epithelial cells.","journal":"Communications Biology","year":2021,"id":170681,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":636888,"name":"Thomas R. Aunins","orcid":"0000-0001-7122-1992","position":1,"is_corresponding":false},{"id":703659,"name":"Colleen M. Courtney","orcid":"0000-0002-2896-4851","position":2,"is_corresponding":false},{"id":704312,"name":"Jocelyn K. Campos","orcid":null,"position":3,"is_corresponding":false},{"id":703660,"name":"Peter B. Otoupal","orcid":"0000-0001-9871-3444","position":4,"is_corresponding":false},{"id":703661,"name":"Keesha E. Erickson","orcid":"0000-0001-7482-457X","position":5,"is_corresponding":false},{"id":703662,"name":"Nancy Madinger","orcid":"0000-0001-6387-618X","position":6,"is_corresponding":false},{"id":636897,"name":"Anushree Chatterjee","orcid":"0000-0002-8389-9917","position":7,"is_corresponding":false},{"id":703658,"name":"Kristen A. Eller","orcid":"0000-0003-2922-5476","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-18T23:46:24.040760Z","pmid":"33712689","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}