Pseudomonas aeruginosa the GbdR Regulon of the Pathogen Liberate and Grab It, Ingest and Digest It:

-trimethylglycine) (Fig. 1) is withoutany doubt the most widely used compatible solute in nature,asmembersofallkingdomsoflifeuseittofendoffthedetrimentaleffects of high osmolarity on cell volume, turgor, cellular physiol-ogy, and growth (1–4). Compatible solutes are operationally de-fined (5) as organic osmolytes that are highly compliant with theproperfunctioningofproteinsandbiochemicalprocesses,aphys-icochemical feature of these compounds that largely stems fromtheir preferential exclusion from the immediate hydration shell ofthe protein backbone (6, 7). This uneven distribution of compat-ible solutes in the cell water generates a thermodynamic drivingforce for proteins and protein complexes to adopt a compact,well-folded native conformation under otherwise denaturingconditions. As a consequence, compatible solutes can be amassedto exceedingly high concentrations without negative side effectson cell physiology; they thereby counteract the osmotically insti-gated efflux of water from the cell and optimize at the same timethesolventpropertiesofthecytoplasm(8,9).Microorganismscanaccumulate compatible solutes either through uptake or throughsynthesiswhentheyareexposedtoosmoticstress.Thisphysiolog-ical trait is widely present both in

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