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DNABII family proteins, primarily consisting of Integration Host Factor (IHF) and Histone-like protein (HU), are highly conserved bacterial nucleoid-associated proteins that serve as essential structural components of the extracellular DNA (eDNA) matrix in biofilms (Goodman et al., 2011). These proteins bind to and stabilize the junctions of bent or crossed DNA strands, acting as the physical "linchpins" that maintain the integrity of the biofilm's protective scaffold (Novotny et al., 2013). In the context of human disease, biofilms significantly enhance bacterial resistance to antibiotics and shield pathogens from the host immune system, leading to chronic infections such as those seen in cystic fibrosis, chronic otitis media, and non-healing wounds (Estelles et al., 2016). Therapeutic strategies targeting DNABII proteins utilize monoclonal antibodies, such as TRL1070, to sequester these proteins from the eDNA matrix. This action causes the rapid physical collapse of the biofilm structure, dispersing the bacteria into a planktonic state where they are highly vulnerable to conventional antibiotics and immune-mediated clearance (Trellis Bioscience, 2024). This approach represents a novel "anti-virulence" strategy that does not directly kill bacteria but instead removes their primary defense mechanism.
Antibody-mediated sequestration of DNABII proteins from the extracellular DNA matrix, resulting in the loss of biofilm structural integrity and increased bacterial susceptibility to antibiotics and immune clearance (Estelles et al., 2016).
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