Bacterial DNABII family protein (DNABII)

Bacterial DNABII family proteins, primarily comprising Integration Host Factor (IHF) and Histone-like protein (HU), are small, basic, DNA-binding proteins that are essential for the structural integrity of bacterial biofilms (Goodman et al., 2011, PubMed: 21613501). While traditionally known for their intracellular roles in nucleoid organization and gene regulation, these proteins are also secreted into the extracellular polymeric substance (EPS) of biofilms. There, they bind to and stabilize the junctions of extracellular DNA (eDNA) lattices, acting as critical 'linchpins' that maintain the three-dimensional architecture of the biofilm (Devaraj et al., 2015, PubMed: 25938842). This structural role protects the resident bacteria from environmental stressors, host immune defenses, and antibiotic penetration, contributing to the chronic nature of many bacterial infections. Targeting DNABII proteins represents a novel therapeutic strategy to combat biofilm-mediated resistance. Monoclonal antibodies, such as the clinical-stage candidate TRL1068, bind to highly conserved epitopes on these proteins, causing them to dissociate from the eDNA scaffold (Estelles et al., 2016, PubMed: 27324718). This dissociation leads to the rapid collapse and dispersal of the biofilm matrix across a wide range of Gram-positive and Gram-negative pathogens, including Staphylococcus aureus and Pseudomonas aeruginosa. Once the biofilm is disrupted, the previously protected bacteria become significantly more susceptible to conventional antimicrobial therapies and clearance by the host immune system, offering a potential solution for recalcitrant infections in conditions like cystic fibrosis and chronic wounds.

Other names

Integration Host Factor (IHF)Histone-like protein (HU)Nucleoid-associated protein (NAP)Biofilm linchpin proteinDNA-binding protein HUDNA-binding protein IHF

Disruption of the biofilm extracellular matrix by sequestering or removing DNABII proteins from extracellular DNA (eDNA) lattices, leading to the collapse of the biofilm architecture and enhanced susceptibility of the released bacteria to antibiotics and host immune clearance (Devaraj et al., 2015, PubMed: 25938842).