Ureteral stents are fraught with problems. A conditioning film attaches to the stent surface within hours of implantation; however, differences between stent types and their role in promoting encrustation and bacterial adhesion and colonization remain to be elucidated. The present work shows that the most common components do not differ between stent types or patients with the same indwelling stent, and contain components that may drive stent encrustation. Furthermore, unlike what was previously thought, the presence of a conditioning film does not increase bacterial adhesion and colonization of stents by uropathogens. Genitourinary cytokeratins are implicated in playing a significant role in conditioning film formation. Overall, stent biomaterial design to date has been unsuccessful in discovering an ideal coating to prevent encrustation and bacterial adhesion. This current study elucidates a more global understanding of urinary conditioning film components. It also supports specific focus on the importance of physical characteristics of the stent and how they can prevent encrustation and bacterial adhesion.

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In tissues with mechanical function, the regulation of remodeling and repair processes is often controlled by mechanosensitive mechanisms; damage to the tissue structure is detected by changes in mechanical stress and strain, stimulating matrix synthesis and repair. While this mechanoregulatory feedback process is well recognized in animals and plants, it is not known whether such a process occurs in bacteria. In Vibrio cholerae, antibiotic-induced damage to the load-bearing cell wall promotes increased signaling by the two-component system VxrAB, which stimulates cell wall synthesis. Here we show that changes in mechanical stress and strain within the cell envelope are sufficient to stimulate VxrAB signaling in the absence of antibiotics. We applied mechanical forces to individual bacteria using three distinct loading modalities: extrusion loading within a microfluidic device, compression, and hydrostatic pressure. In all three cases, VxrAB signaling, as indicated by a fluorescent protein reporter, was increased in cells submitted to greater magnitudes of mechanical loading, hence diverse forms of mechanical stimuli activate VxrAB signaling. Mechanosensitivity of VxrAB signaling was lost following removal of the VxrAB stimulating endopeptidase ShyA, suggesting that VxrAB may not be directly sensing mechanical forces, but instead relies on other factors including lytic enzymes in the periplasmic space. Our findings suggest that mechanical signals play an important role in regulating cell wall homeostasis in bacteria.Significance StatementBiological materials with mechanical function (bones, muscle, etc.) are often maintained through mechanosensitive mechanisms, in which damage-induced reductions in stiffness stimulate remodeling and repair processes that restore mechanical function. Here we show that a similar process can occur in bacteria. We find that mechanical stresses in the bacterial cell envelope (the primary load-bearing structure in bacteria) regulate signaling of a two-component system involved in cell wall synthesis. These findings suggest that the mechanical stress state within the cell envelope can contribute to cell wall homeostasis. Furthermore, these findings demonstrate the potential to use mechanical stimuli to regulate gene expression in bacteria.

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