Bacterial DNABII protein family (DNABII)

The Bacterial DNABII protein family, primarily comprising Histone-like protein (HU) and Integration host factor (IHF), consists of highly conserved DNA-binding proteins that are essential for the structural integrity of bacterial biofilms (Goodman et al., 2011, PNAS). While these proteins traditionally function as nucleoid-associated proteins (NAPs) involved in DNA bending and gene regulation within the bacterial cell, they are also actively secreted into the extracellular space. In the extracellular environment, DNABII proteins bind to and stabilize the scaffold of extracellular DNA (eDNA), acting as linchpins that maintain the integrity of the biofilm protective matrix (Devaraj et al., 2015, Microbiology Spectrum). This matrix protects bacteria from host immune defenses and increases their tolerance to antibiotic treatment by several orders of magnitude. Therapeutic strategies targeting the DNABII family, such as the monoclonal antibody TRL1068, aim to disrupt the biofilm architecture by sequestering these proteins, thereby releasing the bacteria into a planktonic state (Novotny et al., 2020, EBioMedicine). Once dispersed, the bacteria become significantly more susceptible to conventional antibiotic therapies and host immune clearance, offering a promising approach for treating chronic, recalcitrant infections.

Other names

Integration host factorIHFHistone-like proteinHUNucleoid-associated proteinsNAPs

Sequestration or removal of DNABII proteins from the extracellular biofilm matrix, which destabilizes the extracellular DNA (eDNA) scaffold, leading to biofilm collapse and increased susceptibility of bacteria to antibiotics and host immune clearance.