High-mobility group nucleosome-binding domain 2 protein inhibits the invasion of Klebsiella pneumoniae into mouse lungs in vivo

Abstract

Since bacterial invasion into host cells is a critical step in the infection process and the predominance of multiple-antibiotic-resistant Klebsiella (K.) pneumoniae strains, using molecular agents to interfere with K. pneumoniae invasion is an attractive approach for the prevention of infection and suppress the immune inflammatory response. In previous studies by our group, high-mobility group nucleosome-binding domain 2 (HMGN2) protein was shown to exhibit anti-bacterial activity in vitro. The objective of the present study was to investigate the effects of HMGN2 protein on the invasion of K. pneumoniae 03183 in vivo. The results showed that pre-treatment with 128 µg/ml HMGN2 significantly reduced K. pneumoniae 03183 invasion into mouse lungs and increased the mRNA expression of CXCL1 and LCN2 within 2 h. Immunohistochemical staining showed that F-actin expression was significantly decreased, and fluorescence microscopy and western blot analysis further demonstrated that HMGN2 significantly blocked K. pneumoniae 03183-induced actin polymerization. These changes implied that HMGN2 may provide protection against K. pneumoniae 03183 infection in vivo.

Biological Functions of HMGN Chromosomal Proteins

“…The presence of HMGN2 in the cytoplasm and extracellular environment of mononuclear leukocytes highlights the function of HMGN2 as an antimicrobial effector. Full-length HMGN2 also displayed potential antimicrobial activity against E. coli ML-35p, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231 and in vivo, inhibited the invasion of K. pneumoniae 03182 onto mouse lungs [80]. An antimicrobial peptide with the sequence PKRKAEGDAK, which is identical to the nucleosome binding domain of HMGN2 was isolated from human peripheral blood mononuclear leukocytes [81].…”

K. pneumoniae and M. smegmatis infect epithelial cells via different strategies

“…For example, K . pneumoniae can induce a cytotoxic effect in lung epithelial cells with a high MOI ranging from 100:1 to 1,000:1, and also increases Factin protein levels in mouse lung tissue ( 18 , 25 ). Mycobacterial adhere to the host epithelium with MBP-1 protein by interacting with the host cytoskeletal protein vimentin ( 9 ).…”

“…The interaction with host proteins and the modification of host cell signaling are frequent mediators of the capacity of bacteria to adhere to and infiltrate the mucosal epithelium. In response to pathogen invasion, cytokines and chemokines are essential chemicals that play a role in practically every aspect of immunity and inflammation ( 18 , 19 ). It has been determined that interleukin (IL)-6 increases neutrophil death to improve the survival of pneumonia sepsis brought on by K .…”

MicroRNAs for Virus Pathogenicity and Host Responses, Identified in SARS-CoV-2 Genomes, May Play Roles in Viral-Host Co-Evolution in Putative Zoonotic Host Species

“…RAB10 is a small GTPase and regulates intracellular vesicle trafficking [65], and has been linked to Legionella pneumophila infection and replication [66]. HMGN2 binds nucleosomal DNA and is associated with transcriptionally active chromatin; it furthermore has antimicrobial activity against bacteria, viruses, and fungi [67,68], while specific roles in SARS-CoV-2 infection remain to be investigated. TMEM167A is involved in the early part of the secretory pathway, and is a regulator of vesicular trafficking [69,70].…”