DNABII family DNA-binding proteins (DNABII)

DNABII family DNA-binding proteins, primarily comprising Integration Host Factor (IHF) and Histone-like protein (HU), are ubiquitous bacterial proteins that play essential roles in both intracellular genetic regulation and extracellular biofilm stability [1, 6]. Intracellularly, they function as nucleoid-associated proteins (NAPs) that bind and bend DNA to facilitate replication, recombination, and transcription [4, 6]. Extracellularly, these proteins serve as critical structural "linchpins" within the extracellular polymeric substance (EPS), where they stabilize the lattice of extracellular DNA (eDNA) by binding to crossed DNA strands at vertices [1, 8]. This stabilization maintains the structural integrity of mature biofilms, protecting resident bacteria from host immune responses and making them highly resistant to conventional antibiotic therapy [2, 3]. Therapeutic strategies, such as the monoclonal antibody cocktail CMTX-101, target the conserved DNA-binding regions of these proteins to sequester them from the biofilm matrix [3, 8]. This sequestration leads to the rapid collapse of the biofilm architecture, releasing the bacteria and significantly increasing their susceptibility to antibiotics and innate immune clearance [7, 8].

Other names

Integration host factorIHFHistone-like proteinHUNucleoid-associated proteinsNAPsIHF-like proteinsHU-like proteins

Sequestration of DNABII proteins from the biofilm matrix, leading to the collapse of the extracellular DNA lattice and sensitization of bacteria to antibiotics and immune clearance.