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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 <jats:italic>Escherichia coli<\/jats:italic>, extended-spectrum beta-lactamase <jats:italic>Klebsiella pneumoniae<\/jats:italic>, New Delhi Metallo-beta-lactamase-1 carrying <jats:italic>Klebsiella pneumoniae<\/jats:italic>, and MDR <jats:italic>Salmonella enterica<\/jats:italic>. 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 <jats:italic>Salmonella<\/jats:italic> infection in human epithelial cells.<\/jats:p>","DOI":"10.1038\/s42003-021-01856-1","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T11:07:02Z","timestamp":1615547222000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Facile accelerated specific therapeutic (FAST) platform develops antisense\u00a0therapies to counter multidrug-resistant bacteria"],"prefix":"10.1038","volume":"4","author":[{"given":"Kristen A.","family":"Eller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Aunins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Courtney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn K.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Otoupal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keesha E.","family":"Erickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy E.","family":"Madinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anushree","family":"Chatterjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"1856_CR1","unstructured":"United States center for disease control. 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