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Paper

TESTING March 03, 2026

The Integration Host Factor is a pH-responsive protein that switches from DNA bending to DNA bridging in acidic biofilm-like conditions

Authors

Dinesh Parthasarathy, Saminathan Ramakrishnan, Georgia Tsang, Auro Varat Patnaik, Sabrina M. C. Hardy, Willem Vanderlinden, Jamieson Howard, Braden Bylett, James R. Law, Mark Leake, Agnes Noy, Davide Michieletto

Abstract

The Integration Host Factor (IHF) is a nucleoid-associated protein critical for both DNA compaction and biofilm stability. While its role in DNA packaging within the cell is well understood, its structural role in scaffolding biofilms is more puzzling and difficult to reconcile with its known DNA bending activity. Here, we investigated how IHF-DNA interactions are modulated across a pH spectrum mimicking the acidic microenvironments of bacterial biofilms. By performing all-atom calculations we discovered that low pHs lead to a change in protonation of IHF residues, which in turn exposes positively charged patches. We then conjectured that these positively charged residues could lead to intermolecular DNA bridging and tested this hypothesis through single-molecule and bulk assays. We discovered that while at physiological pH IHF mostly bends DNA, at pH < 5 there is clear evidence of IHF-mediated intermolecular crosslinking. Our results demonstrate that pH significantly modulates IHF-DNA interactions and explains the structural role played by IHF in supporting biofilm mechanics through intermolecular crosslinking.

Metadata

arXiv ID: 2603.03466
Provider: ARXIV
Primary Category: cond-mat.soft
Published: 2026-03-03
Fetched: 2026-03-05 06:06

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