Phosphorylation of the prokaryotic histone-like protein H-NS modulates bacterial virulence in Salmonella Typhimurium

• Published in: Microbiological research Vol. 292; p. 128041
• Main Authors: Wang, Ying, Ge, Jinli, Xian, Wei, Tang, Zhiheng, Xue, Baoshuai, Yu, Jingchen, Yao, Yu-Feng, Liu, Huwei, Qiu, Jiazhang, Liu, Xiaoyun
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.03.2025
• Subjects: Bacterial effectors; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation, Bacterial; H-NS; Histones - metabolism; Humans; Phosphorylation; Protein Processing, Post-Translational; Salmonella Infections - microbiology; Salmonella typhimurium - genetics; Salmonella typhimurium - metabolism; Salmonella typhimurium - pathogenicity; Samonella typhimurium; Type III Secretion Systems - genetics; Type III Secretion Systems - metabolism; Virulence; Virulence - genetics; Bacterial effectors; Phosphorylation; H-NS; Virulence; Samonella typhimurium
• ISSN: 0944-5013; 1618-0623; 1618-0623
• DOI: 10.1016/j.micres.2024.128041

H-NS is a prokaryotic histone-like protein that binds to bacterial chromosomal DNA with important regulatory roles in gene expression. Unlike histone proteins, hitherto post-translational modifications of H-NS are still largely uncharacterized, especially in bacterial pathogens. Salmonella Typhimurium is a primary enteric pathogen and its virulence is mainly dependent on specialized type III secretion systems (T3SSs), which were evolutionarily acquired via horizontal gene transfer. Previous studies have shown that H-NS plays a critical role in silencing foreign T3SS genes. Here, we found that H-NS is phosphorylated at multiple residues in S. Typhimurium, including S45, Y61, S78, S84, T86, and T106. Notably, we demonstrated that phosphorylation of H-NS S78 promotes its dissociation from DNA via a mechanism dependent on dimer formation, thereby leading to transcriptional activation of target genes. Functionally, phosphoryl-H-NS contributes to the expression of T3SS-associated proteins and hence increases bacterial virulence during infection. Therefore, our study reveals a novel mechanism by which covalent modifications of prokaryotic histone-like proteins regulate bacterial virulence of an important human pathogen.