DNABII family bacterial DNA-binding proteins (DNABII)

The DNABII family of bacterial DNA-binding proteins, primarily comprising integration host factor (IHF) and histone-like protein (HU), are essential components of both the bacterial nucleoid and the extracellular biofilm matrix. Intracellularly, they function as nucleoid-associated proteins that regulate DNA architecture, replication, and gene expression. Extracellularly, they act as structural linchpins that stabilize the lattice of extracellular DNA (eDNA) in biofilms, which protects bacteria from environmental stressors and host defenses. Because these proteins are highly conserved across nearly all eubacteria and lack mammalian homologs, they are ideal targets for pathogen-agnostic biofilm disruption. Therapeutic agents like monoclonal antibodies target the DNA-binding domains of these proteins to induce biofilm collapse, thereby resensitizing bacteria to antibiotics and the innate immune system.

Other names

Integration host factor (IHF)Histone-like protein (HU)Nucleoid-associated proteins (NAPs)Bacterial histone-like proteinsDNA-binding protein HUIntegration host factor subunit alphaIntegration host factor subunit beta

Sequestration of DNABII proteins from the extracellular matrix induces an equilibrium shift that causes bound proteins to dissociate from extracellular DNA (eDNA), leading to the structural collapse of the biofilm and the release of bacteria into a planktonic state susceptible to antibiotics and immune clearance.