{"publication_status":"published","author":[{"first_name":"Florian","full_name":"Buchholz, Florian","last_name":"Buchholz"},{"full_name":"Upterworth, Lina M.","first_name":"Lina M.","last_name":"Upterworth"},{"last_name":"Tueffers","full_name":"Tueffers, Leif","first_name":"Leif"},{"last_name":"Groth","first_name":"Espen E.","full_name":"Groth, Espen E."},{"full_name":"Haas, Kira","first_name":"Kira","last_name":"Haas"},{"last_name":"Schütz","first_name":"Daniel","full_name":"Schütz, Daniel"},{"last_name":"Savietto Scholz","full_name":"Savietto Scholz, Abigail","first_name":"Abigail"},{"full_name":"Batra, Aditi","first_name":"Aditi","last_name":"Batra"},{"last_name":"Pal","first_name":"Surajit","full_name":"Pal, Surajit"},{"full_name":"Banerjee, Samarpita","first_name":"Samarpita","last_name":"Banerjee"},{"full_name":"Dubey, Badri N.","first_name":"Badri N.","last_name":"Dubey"},{"last_name":"Franzenburg","full_name":"Franzenburg, Sören","first_name":"Sören"},{"full_name":"Kalsdorf, Barbara","first_name":"Barbara","last_name":"Kalsdorf"},{"first_name":"Klaus F.","full_name":"Rabe, Klaus F.","last_name":"Rabe"},{"first_name":"Dennis","full_name":"Nurjadi, Dennis","last_name":"Nurjadi"},{"first_name":"Jan","full_name":"Rupp, Jan","last_name":"Rupp"},{"first_name":"Dan I.","full_name":"Andersson, Dan I.","last_name":"Andersson"},{"full_name":"Sondermann, Holger","first_name":"Holger","last_name":"Sondermann"},{"last_name":"Bramkamp","first_name":"Marc","full_name":"Bramkamp, Marc"},{"id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","orcid":"0000-0001-9480-5261","full_name":"Römhild, Roderich","last_name":"Römhild"},{"last_name":"Schulenburg","full_name":"Schulenburg, Hinrich","first_name":"Hinrich"}],"DOAJ_listed":"1","type":"journal_article","article_number":"4487","OA_place":"publisher","quality_controlled":"1","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","status":"public","acknowledgement":"We are very grateful to S. Hernando-Amado (Madrid, Spain), C. Pál (Szeged, Hungary), and T. Bollenbach (Cologne, Germany) for critical comments and advice on the manuscript. We further thank D. Rogers, J. Summers (Ploen, Germany) for guidance in allelic exchange, P. Rainey (Ploen, Germany) for providing the plasmids and strains, then J. Lorenzen, K. Flinder, N. Steinbach, S. Butze (all Schulenburg lab), and L. Kirchhoff (Rupp lab) for supporting the experimental work, and also the Rupp and Schulenburg groups for general feedback. We are grateful for financial support from the German Research Foundation within the Research and Training Group 2501 (RTG 2501) on Translational Evolutionary Research (project 4.2 to H.S.), within the Excellence cluster Precision Medicine in chronic Inflammation (PMI; funding under Germany’s Excellence Strategy EXC 2167-390884018, to B.K., K.R., J.R., H.S.), within the Clinician Scientist Program in Evolutionary Medicine (CSEM) – project number 413490537 (to EEG), and as part of the individual grants SCHU 1415/12-2 (to H.S.) and BR-2915/7-1 (to M.B.). We are grateful for financial support from the Swedish Research Council, project number 2021-02091 (to D.I.A.). We are also grateful for financial support from the Max-Planck Society (Fellowship to H.S.), the Leibniz Association within the Leibniz Science-Campus Evolutionary Medicine of the Lung (EvoLUNG, to H.S.), and the project SKILLED funded by the DAMP foundation (to J.R., H.S.). This work was also supported by the ZMB Young Scientist award and the FWF grant 10.55776/ESP219 (to R.R.) and the TransEvo Innovation prize (to F.B.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Open Access funding enabled and organized by Projekt DEAL.\r\n","doi":"10.1038/s41467-026-71178-5","intvolume":"        17","publisher":"Springer Nature","project":[{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","grant_number":"E219","name":"Non-canonical antibiotic interactions"}],"department":[{"_id":"CaGu"}],"PlanS_conform":"1","citation":{"ista":"Buchholz F, Upterworth LM, Tueffers L, Groth EE, Haas K, Schütz D, Savietto Scholz A, Batra A, Pal S, Banerjee S, Dubey BN, Franzenburg S, Kalsdorf B, Rabe KF, Nurjadi D, Rupp J, Andersson DI, Sondermann H, Bramkamp M, Römhild R, Schulenburg H. 2026. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. Nature Communications. 17, 4487.","mla":"Buchholz, Florian, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.” <i>Nature Communications</i>, vol. 17, 4487, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-71178-5\">10.1038/s41467-026-71178-5</a>.","ieee":"F. Buchholz <i>et al.</i>, “Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026.","chicago":"Buchholz, Florian, Lina M. Upterworth, Leif Tueffers, Espen E. Groth, Kira Haas, Daniel Schütz, Abigail Savietto Scholz, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71178-5\">https://doi.org/10.1038/s41467-026-71178-5</a>.","apa":"Buchholz, F., Upterworth, L. M., Tueffers, L., Groth, E. E., Haas, K., Schütz, D., … Schulenburg, H. (2026). Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-71178-5\">https://doi.org/10.1038/s41467-026-71178-5</a>","short":"F. Buchholz, L.M. Upterworth, L. Tueffers, E.E. Groth, K. Haas, D. Schütz, A. Savietto Scholz, A. Batra, S. Pal, S. Banerjee, B.N. Dubey, S. Franzenburg, B. Kalsdorf, K.F. Rabe, D. Nurjadi, J. Rupp, D.I. Andersson, H. Sondermann, M. Bramkamp, R. Römhild, H. Schulenburg, Nature Communications 17 (2026).","ama":"Buchholz F, Upterworth LM, Tueffers L, et al. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-71178-5\">10.1038/s41467-026-71178-5</a>"},"volume":17,"file_date_updated":"2026-06-02T07:11:12Z","_id":"21928","oa_version":"Published Version","oa":1,"date_published":"2026-05-20T00:00:00Z","month":"05","ddc":["570"],"date_updated":"2026-06-02T07:14:35Z","publication":"Nature Communications","date_created":"2026-05-31T22:02:12Z","title":"Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope","day":"20","year":"2026","article_type":"original","scopus_import":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"file_name":"2026_NatureComm_Buchholz.pdf","checksum":"aa29f8806908dc0469dff21e2d5ad01f","creator":"dernst","content_type":"application/pdf","success":1,"file_id":"21936","relation":"main_file","file_size":1276166,"date_updated":"2026-06-02T07:11:12Z","date_created":"2026-06-02T07:11:12Z","access_level":"open_access"}],"OA_type":"gold","publication_identifier":{"eissn":["2041-1723"]},"abstract":[{"text":"Antibiotic combination in time and space is a key strategy to combat antimicrobial resistance. The success of such treatment designs requires their robust efficacy across treatment conditions and a pathogen’s genomic diversity. This study found that an initial treatment with a β-lactam antibiotic causes robust cellular sensitization towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas aeruginosa, including resistant strains. This phenomenon of cellular sensitization, termed negative hysteresis, is modulated by the Cpx envelope stress response system and linked to membrane stress during growth. The increase in efficacy is achieved through a β-lactam induced elevated cellular uptake of the subsequently administered aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases to the expression of synergistic drug interactions, thus enhancing efficacy of antibiotic combinations. Overall, our study identifies the phenomenon of negative hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing antimicrobial therapy.","lang":"eng"}],"language":[{"iso":"eng"}],"corr_author":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"}}