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Neisseria integration host factor (IHF) is a small, heterodimeric DNA-binding protein belonging to the DNABII family, which also includes histone-like proteins (HU). In Neisseria species, such as Neisseria gonorrhoeae and Neisseria meningitidis, IHF functions as a nucleoid-associated protein (NAP) that induces sharp bends in DNA to facilitate essential processes including transcription, site-specific recombination, and DNA replication [1, 3]. It is a critical regulator of virulence, acting as a transcriptional co-activator for the pilE gene, which encodes the major subunit of Type IV pili required for host cell adherence and colonization [1, 4]. Additionally, IHF is a key structural component of the extracellular polymeric substance (EPS) in bacterial biofilms, where it stabilizes the extracellular DNA (eDNA) lattice by acting as a molecular linchpin at DNA crossovers [9, 10]. This extracellular role has made IHF a primary target for anti-biofilm therapies, such as the monoclonal antibody CMTX-101, which sequesters IHF to trigger biofilm collapse and restore bacterial susceptibility to antibiotics and host immune responses [8, 9].
Sequestration of DNABII proteins (IHF/HU) from the biofilm matrix, leading to the destabilization of the extracellular DNA (eDNA) lattice and subsequent biofilm collapse.
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