LAUSR

Significance Histone-like protein from Escherichia coli strain U93 (HU) protein is the most abundant nucleoid-associated protein in bacteria, which plays a fundamental role in chromosomal compaction and organization. It is essential for most bacteria as well as Apicomplexans, thus an important target for the development of antimicrobial and antimalaria drugs. We report Gp46 as a phage protein HU inhibitor. It inhibits HU of Bacillus subtilis by occupying its DNA binding site, thus preventing chromosome segregation during cell division. As key residues for the interaction are highly conserved, Gp46 interacts with HUs of a broad range of pathogens, including many pathogenic bacteria and Apicomplexan parasites like Plasmodium falciparum. Thus, this cross-species property could benefit antibiotic and antimalaria drug development that targets HU.