2026-06-23 スイス連邦工科大学ローザンヌ校（EPFL）
Physical pressure helps the pathogenic bacterium Pseudomonas aeruginosa survive antibiotic treatment. ©iStock
＜関連情報＞
- https://actu.epfl.ch/news/squeezed-bacteria-are-harder-to-kill/
- https://www.pnas.org/doi/10.1073/pnas.2605176123
隔離された環境での増殖は、緑膿菌の抗生物質耐性を促進する Growth in confinement promotes Pseudomonas aeruginosa tolerance to antibiotics
Sourabh Monnappa, Zainebe Al-Mayyah, Mahmut Selman Sakar, and Alexandre Persat
Proceedings of the National Academy of Sciences Published: May 29, 2026
DOI:https://doi.org/10.1073/pnas.2605176123
Significance
During host colonization or infection, bacteria encounter spatially constrained environments, such as deep-seated infected tissues or abscesses that impose mechanical stress. As they grow under confinement, they generate internal forces whose magnitude depends on the mechanical properties of the surrounding environment, but how these properties impact pathogen survival remains unclear. Here, we demonstrate that substrate stiffness directly governs bacterial survival to antibiotic treatments. Increased stiffness enhances tolerance through an active adaptation to growth-induced pressure that remodels bacterial membrane and ion-transport complex. Our findings establish mechanical forces as a determinant of antibiotic resilience and uncover innovative therapeutic strategies based on bacterial–material interactions. They also open opportunities to design new biomaterials to block colonization and infections.
Abstract
Bacteria often proliferate within confined spaces imposed by host tissues, extracellular matrices, or their own biofilms where cells press against surrounding materials and experience elevated mechanical stress. Whether these forces influence pathogen physiology and fitness remains unresolved. We show that Pseudomonas aeruginosa adapts to mechanical confinement by increasing resilience to antibiotics. Using synthetic hydrogels of tunable stiffness that restrict expansion without limiting nutrient access, we demonstrate that growth in elastic materials reduces P. aeruginosa sensitivity to antibiotics in a stiffness-dependent manner. Although slower growth contributes to tolerance, Tn-seq under colistin and tobramycin treatment identified key regulators of mechanically induced tolerance. We found that active efflux mediated by sodium–proton Sha antiporters, together with protective remodeling of the bacterial membrane, enhances the resilience of confined populations without impacting growth. These findings reveal that P. aeruginosa adapts to mechanical stress in ways that may promote treatment failure even in the absence of intrinsic resistance.
