Integration host factor (IHF)

Integration host factor (IHF) is a small, heterodimeric nucleoid-associated protein (NAP) primarily found in Gram-negative bacteria, consisting of alpha (IHFα) and beta (IHFβ) subunits [6, 11]. It functions as a global architectural and regulatory protein that binds to specific DNA sequences, inducing sharp bends (exceeding 160 degrees) to facilitate processes such as site-specific recombination, DNA replication, and transcription [7, 10, 31]. Beyond its intracellular roles, IHF is a critical structural component of the extracellular DNA (eDNA) matrix in bacterial biofilms, where it stabilizes the mesh-like framework that protects pathogens from the host immune system and antibiotics [1, 2, 3]. Therapeutic strategies targeting IHF, such as the humanized monoclonal antibodies CMTX-101 and TRL1068, aim to destabilize this biofilm matrix by sequestering IHF, leading to its rapid collapse and the release of bacteria into a more susceptible planktonic state [23, 24, 25]. This approach has shown promise in enhancing the efficacy of traditional antibiotics against chronic and recurrent infections, including those caused by Haemophilus influenzae, Pseudomonas aeruginosa, and Escherichia coli [2, 24, 25]. By targeting a broadly conserved structural element, IHF-directed therapies offer a pathogen-agnostic method to combat antimicrobial resistance and improve treatment outcomes for biofilm-mediated diseases [23, 26].

Other names

DNABII family proteinNucleoid-associated proteinHistone-like proteinHimA (alpha subunit)HimD (beta subunit)IHFalphaIHFbeta

Biofilm disruption by sequestering IHF from the extracellular DNA (eDNA) matrix, leading to structural collapse of the biofilm and increased bacterial susceptibility to antibiotics and host immune clearance [2, 23, 25].