{"doi":"10.1101/2022.04.06.487411","title":"Mechanical morphotype switching as an adaptive response in mycobacteria","abstract":"Abstract Invading microbes face a myriad of cidal mechanisms of phagocytes that inflict physical damage to microbial structures. How intracellular bacterial pathogens adapt to these stresses is not fully understood. Here, we report a new virulence mechanism by which mycobacteria alter the mechanical stiffness of their cell surface to become refractory to killing during infection. Long-Term Time-Lapse Atomic Force Microscopy was used to reveal a process of “mechanical morphotype switching” in mycobacteria exposed to host intracellular stress. A “soft” mechanical morphotype switch enhances tolerance to intracellular macrophage stress, including cathelicidin. Genetic manipulation, by deletion of uvrA , or pharmacological treatment, with bedaquiline, locked mycobacteria into a “soft” mechanical morphotype state, enhancing survival in macrophages. Our study proposes microbial mechanical adaptation as a new axis for surviving host-mediated stressors. One-Sentence Summary Bacteria alter their cell surface mechanical properties to increase survival during macrophage infection.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303123,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":816234,"name":"Yuxiang Chen","orcid":"0000-0002-3231-2047","position":1,"is_corresponding":false},{"id":995154,"name":"Chiara Toniolo","orcid":"0000-0002-2167-2936","position":2,"is_corresponding":false},{"id":435691,"name":"Juan M. Belardinelli","orcid":"0000-0003-1336-9141","position":3,"is_corresponding":false},{"id":671920,"name":"Zuzana Palčeková","orcid":"0000-0003-4045-7008","position":4,"is_corresponding":false},{"id":842159,"name":"Paul D. Ashby","orcid":"0000-0003-4195-310X","position":5,"is_corresponding":false},{"id":995155,"name":"Georg E. Fantner","orcid":"0000-0001-5889-3022","position":6,"is_corresponding":false},{"id":363356,"name":"Mary Jackson","orcid":"0000-0002-9212-0258","position":7,"is_corresponding":false},{"id":995156,"name":"John D. McKinney","orcid":"0000-0002-0557-3479","position":8,"is_corresponding":false},{"id":816235,"name":"Babak Javid","orcid":"0000-0002-6354-6305","position":9,"is_corresponding":false},{"id":235407,"name":"Haig Alexander Eskandarian","orcid":"0000-0002-0610-0550","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T00:32:20.348385Z","pmid":null,"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":[]}