Geometric constraint-triggered collagen expression mediates bacterial-host adhesion

TL;DR: Environmental osmotic pressure remodels host cell collagen subtypes, enhancing bacterial adhesion force via nonlinear mechanisms, with collagen XV and II overexpression linked to increased adhesion under hypotonic and hypertonic conditions, respectively.

Abstract: Abstract Bacteria often proliferate within confined spaces imposed by host tissues, extracellular matrices, or their own biofilms. In such environments, cells press against surrounding materials and experience elevated mechanical stress, but whether these forces influence pathogen physiology and fitness remains unclear. Here, we show that Pseudomonas aeruginosa adapts to mechanical confinement by increasing resilience to antibiotics. Using synthetic hydrogels of tunable stiffness that restrict physical expansion without limiting nutrient access, we demonstrate that growth in elastic materials reduces P. aeruginosa sensitivity to multiple clinically relevant antibiotics in a stiffness-dependent manner. Although slower growth contributes to this decreased susceptibility, Tn-seq under antibiotic treatment identified key regulators of mechanically induced tolerance. We find 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 antibiotic resistance.

TL;DR: Environmental osmotic pressures modulate bacterial-host adhesion through collagen remodeling. Osmoregulated overexpression of collagen subtypes drives the adhesion force increase.

TL;DR: A detailed protocol is presented for Smart-seq2 that allows the generation of full-length cDNA and sequencing libraries by using standard reagents and the lack of strand specificity and the inability to detect nonpolyadenylated (polyA−) RNA.

TL;DR: In this article, a method to determine the spring constant of a rectangular atomic force microscope cantilever is proposed that relies solely on the measurement of the resonant frequency and quality factor of the cantilevers in fluid (typically air), and knowledge of its plan view dimensions.

TL;DR: The cell-matrix and cell-cell adhesion, protease, and cytokine systems that underlie tissue invasion by cancer cells are described and explained to explain how the reciprocal reprogramming of both the tumor cells and the surrounding tissue structures not only guides invasion, but also generates diverse modes of dissemination.

TL;DR: The stiffness of tissue components — from extracellular matrix and single cells to bulk tissue — is outlined, and how this understanding facilitates the engineering of materials with lifelike properties is discussed.