Histone-like protein (HU)

Histone-like proteins, primarily represented by the HU (Heat-unstable) protein family, are small, basic, DNA-binding proteins that serve as the primary architectural components of the bacterial nucleoid. They are functional analogs to eukaryotic histones, responsible for compacting the bacterial chromosome through DNA bending, wrapping, and the induction of negative supercoiling. Beyond their structural role, these proteins act as global transcriptional regulators that modulate the expression of genes essential for virulence, metabolism, and adaptation to environmental stress. In many pathogenic species, such as Mycobacterium tuberculosis and Vibrio cholerae, histone-like proteins are indispensable for survival and the development of drug-tolerant subpopulations. Additionally, they are critical for the integrity of biofilms, where they stabilize the lattice of extracellular DNA (eDNA) within the matrix. Therapeutic approaches currently under investigation include monoclonal antibodies that disrupt biofilm structures and small-molecule inhibitors that target the protein's DNA-binding or dimerization interfaces. Because these proteins are structurally distinct from human histones, they are considered high-value targets for the development of novel, narrow-spectrum antimicrobial therapies.

Other names

Heat-unstable proteinNucleoid-associated proteinDNABII family proteinHistone-like nucleoid-structuring proteinH-NSIntegration host factorIHFFactor for inversion stimulationFisHlpAHBsuHupBLsr2

Inhibition of DNA binding, disruption of protein dimerization, perturbation of nucleoid architecture, and destabilization of the extracellular biofilm matrix.