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DNABII family proteins, primarily consisting of Integration Host Factor (IHF) and Histone-like protein (HU), are highly conserved, small, basic proteins that function as nucleoid-associated proteins (NAPs) across nearly all bacterial species (Goodman et al., 1999, PubMed). While they are essential for intracellular processes such as DNA replication, recombination, and transcriptional regulation, they also play a critical role in the extracellular environment as structural components of bacterial biofilms (Novotny et al., 2013, PNAS). These proteins bind to and bend extracellular DNA (eDNA) at specific or non-specific sites, acting as essential linchpins that stabilize the physical matrix of the biofilm (Brockson et al., 2014, Molecular Microbiology). Because the biofilm matrix protects bacteria from both host immune defenses and antibiotic penetration, the presence of DNABII proteins is a key factor in the persistence of chronic infections. Therapeutic strategies, such as the monoclonal antibody TRL1068, target these proteins to trigger the rapid collapse of the biofilm structure (Trellis Bioscience, 2024). This dispersal converts protected sessile bacteria into vulnerable planktonic forms, significantly enhancing the efficacy of co-administered conventional antibiotics in treating recalcitrant infections like cystic fibrosis and prosthetic joint infections (Gustave et al., 2013, Journal of Infectious Diseases).
Sequestration and removal of DNABII proteins from the extracellular DNA (eDNA) scaffold within the bacterial biofilm matrix, resulting in the loss of structural integrity, biofilm collapse, and the release of bacteria into a planktonic state that is susceptible to antibiotics and host immune clearance.
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