Bacterial histone-like protein HU (HU)

Bacterial histone-like protein HU is a small, basic, and highly conserved nucleoid-associated protein (NAP) that plays a fundamental role in the architectural organization of the bacterial genome [1, 7, 12]. It functions by binding to double-stranded DNA, particularly at distorted sites such as nicks, gaps, and kinks, where it induces significant DNA bending and compaction to fit the chromosome within the cell [4, 5, 17]. Beyond its structural duties, HU is a critical regulator of essential cellular processes, including DNA replication initiation, recombination, repair, and the transcription of genes involved in stress response and virulence [12, 16]. In several major pathogens, including Mycobacterium tuberculosis and Streptococcus pneumoniae, HU is essential for survival, positioning it as a promising target for the development of novel antibiotics [1, 3, 16]. Therapeutic strategies targeting HU focus on small molecules, such as stilbene derivatives and epigallocatechin gallate (EGCG), which disrupt its ability to bind DNA and consequently collapse the nucleoid structure [1, 2]. Additionally, HU has been identified as a molecular glue that stabilizes the extracellular DNA matrix in bacterial biofilms, suggesting that its inhibition could also impair biofilm-mediated antibiotic resistance [2, 15]. While HU is structurally distinct from eukaryotic histones, a primary challenge in drug development is ensuring high specificity to avoid potential cross-reactivity with human DNA-binding proteins [3, 5]. Ongoing research continues to explore HU's role in host-pathogen interactions and its potential as a broad-spectrum antimicrobial target [2, 10].

Other names

DNA-binding protein HUHeat-unstable proteinNucleoid-associated protein HUHlpAHBhupAhupB

Inhibition of DNA binding and compaction, leading to disruption of nucleoid architecture, impairment of chromosome segregation, and attenuation of bacterial virulence or biofilm integrity [1, 2, 3, 15].