{"doi":"10.1016/j.celrep.2020.02.033","title":"Synthetic Cassettes for pH-Mediated Sensing, Counting, and Containment","abstract":"As pH is fundamental to all biological processes, pH-responsive bacterial genetic circuits enable precise sensing in any environment. Where the unintentional release of engineered bacteria poses a concern, coupling pH sensing to the expression of a toxin creates an effective bacterial containment system. Here, we present a pH-sensitive kill switch (acidic termination of replicating population [acidTRP]), based on the Escherichia coli asr promoter, with a survival ratio of <1 in 106. We integrate acidTRP with cryodeath to produce a 2-factor containment system with a combined survival ratio of <1 in 1011 while maintaining evolutionary stability. We further develop a pulse-counting circuit with single-cell readout for each administered stimulus pulse. We use this pulse counter to record multiple pH changes and combine it with acidTRP to make a 2-count acid-sensitive kill switch. These results demonstrate the ability to build complex genetic systems for biological containment.","journal":"Cell Reports","year":2020,"id":59956,"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":64,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":316324,"name":"Alexander D. Naydich","orcid":null,"position":1,"is_corresponding":false},{"id":316325,"name":"Juliet Bramante","orcid":null,"position":2,"is_corresponding":false},{"id":316326,"name":"Rachel Barocio","orcid":null,"position":3,"is_corresponding":false},{"id":316327,"name":"Michael Certo","orcid":null,"position":4,"is_corresponding":false},{"id":316328,"name":"Hannah Wellington","orcid":null,"position":5,"is_corresponding":false},{"id":316329,"name":"Elizabeth Redfield","orcid":null,"position":6,"is_corresponding":false},{"id":315626,"name":"Samuel O’Keefe","orcid":"0000-0002-3037-5212","position":7,"is_corresponding":false},{"id":315627,"name":"Sherry Shiqian Gao","orcid":"0000-0002-8340-5737","position":8,"is_corresponding":false},{"id":316330,"name":"Adam Cusolito","orcid":null,"position":9,"is_corresponding":false},{"id":315628,"name":"Jeffrey C. Way","orcid":"0000-0002-6676-3188","position":10,"is_corresponding":false},{"id":315629,"name":"Pamela A. Silver","orcid":"0000-0002-7856-4071","position":11,"is_corresponding":false},{"id":316323,"name":"Finn Stirling","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T21:08:26.834549Z","pmid":"32130913","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":[]}