Target intelligence / Profile preview

Neisseria integration host factor (IHF)

Target
IHF
Molecular classification
DNA-binding protein, Transcription factor, Nucleoid-associated protein, DNABII family protein
01

Overview

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].

Other names
IHFIntegration host factorDNABII proteinIHF-alpha/beta heterodimerihfA/ihfB gene product
02

Mechanism of action

Sequestration of DNABII proteins (IHF/HU) from the biofilm matrix, leading to the destabilization of the extracellular DNA (eDNA) lattice and subsequent biofilm collapse.

03

Biological functions

DNA bendingTranscription regulationBiofilm formationDNA replicationGenetic recombinationNucleoid compaction
04

Disease associations

InfectionGonorrheaMeningitisBiofilm-associated infection
05

Safety considerations

Risk of systemic dissemination of bacteria upon biofilm disruptionTherapeutic challenge of ensuring antibiotic coverage during biofilm collapsePotential for cross-reactivity with commensal bacterial species
06

Interacting drugs

CMTX-101

1 more in the full profile.

07

Biomarkers

Extracellular DNA (eDNA) levelsDNABII protein expression in clinical isolates

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