{"doi":"10.1073/pnas.2216774120","title":"Shear rate sensitizes bacterial pathogens to H <sub>2</sub> O <sub>2</sub> stress","abstract":"Cells regularly experience fluid flow in natural systems. However, most experimental systems rely on batch cell culture and fail to consider the effect of flow-driven dynamics on cell physiology. Using microfluidics and single-cell imaging, we discover that the interplay of physical shear rate (a measure of fluid flow) and chemical stress trigger a transcriptional response in the human pathogen Pseudomonas aeruginosa . In batch cell culture, cells protect themselves by quickly scavenging the ubiquitous chemical stressor hydrogen peroxide (H 2 O 2 ) from the media. In microfluidic conditions, we observe that cell scavenging generates spatial gradients of H 2 O 2 . High shear rates replenish H 2 O 2 , abolish gradients, and generate a stress response. Combining mathematical simulations and biophysical experiments, we find that flow triggers an effect like “wind-chill” that sensitizes cells to H 2 O 2 concentrations 100 to 1,000 times lower than traditionally studied in batch cell culture. Surprisingly, the shear rate and H 2 O 2 concentration required to generate a transcriptional response closely match their respective values in the human bloodstream. Thus, our results explain a long-standing discrepancy between H 2 O 2 levels in experimental and host environments. Finally, we demonstrate that the shear rate and H 2 O 2 concentration found in the human bloodstream trigger gene expression in the blood-relevant human pathogen Staphylococcus aureus , suggesting that flow sensitizes bacteria to chemical stress in natural environments.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":323262,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":997063,"name":"Alexander M. Shuppara","orcid":"0000-0002-0838-637X","position":1,"is_corresponding":false},{"id":997657,"name":"Anuradha Sharma","orcid":null,"position":2,"is_corresponding":false},{"id":582781,"name":"Matthias D. Koch","orcid":"0000-0003-4408-9900","position":3,"is_corresponding":false},{"id":997064,"name":"Jessica-Jae S. Palalay","orcid":"0009-0009-9400-7134","position":4,"is_corresponding":false},{"id":351248,"name":"Jana N. Radin","orcid":"0000-0003-1783-7336","position":5,"is_corresponding":false},{"id":331762,"name":"Thomas E. Kehl‐Fie","orcid":"0000-0001-8234-1113","position":6,"is_corresponding":false},{"id":274314,"name":"James A. Imlay","orcid":"0000-0001-5266-7403","position":7,"is_corresponding":false},{"id":939915,"name":"Joseph E. Sanfilippo","orcid":"0000-0002-8775-5179","position":8,"is_corresponding":false},{"id":644920,"name":"Gilberto C. Padron","orcid":"0000-0002-5006-9159","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:07:52.377944Z","pmid":"36888662","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":[]}