Multi-Temperature ITC Panel (15/25/37C) Measuring Both DeltaCp and DeltaH Temperature Sensitivity Simultaneously Provides a Single Biophysical Test for UTI Phage Selection

Isothermal titration calorimetry — ITC for short — is a laboratory technique that measures heat released or absorbed when two molecules bind together, like a virus latching onto a bacterial cell. By measuring this heat precisely, scientists can calculate how tightly and how favorably that binding occurs. Meanwhile, phage therapy is a century-old idea experiencing a major comeback: instead of antibiotics, you use bacteriophages — viruses that naturally hunt and kill bacteria — to treat infections. The challenge with urinary tract infections (UTIs) is that urine is a wildly unpredictable environment: it can be dilute and watery or extremely concentrated depending on how hydrated the patient is, and during a fever, body temperature shifts in ways that can change how well a virus binds to its bacterial target. This hypothesis proposes a clever shortcut: instead of running multiple separate tests to evaluate different phage candidates, run one ITC experiment at three temperatures — 15°C, 25°C, and 37°C — and extract two critical numbers from the same dataset. The first number (called ΔCp, or heat capacity change) tells you whether the phage's binding is driven by water-repelling hydrophobic forces, which tend to be stable even when salt concentration in urine swings wildly. The second number (the ratio of binding enthalpy to free energy at body temperature) tells you whether the binding will hold up during a fever. Phages that pass both thresholds — binding driven mostly by hydrophobic forces AND entropy rather than raw heat exchange — are theoretically the most robust candidates for febrile UTI patients. The elegance here is efficiency: one experimental panel, two clinically meaningful predictions, zero extra experiments. It's the biophysical equivalent of a two-for-one diagnostic. If the correlations hold, a lab could screen a library of phage candidates and quickly shortlist the ones most likely to work in the messy, variable environment of a real human urinary tract.

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