a-precise-pathogen-delivery-recovery-system-for-murine-models

A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia

Secondary bacterial pneumonias following influenza infections consistently rank within the top ten leading causes of death in the United States. To date, ...

Montana State University

Staphylococcus aureus is a predominant cause of fatal pneumonia following influenza A virus (IAV) infection. Herein we investigate the influence of antecedent IAV infection on S. aureus virulence gene expression. Using a murine model, comparing the USA300 and USA300ΔsaeR/S strains, we demonstrate that S. aureus pathogenesis following IAV infection is SaeR/S dependent. Furthermore, we show that IAV modulates the lung environment to rapidly up-regulate S. aureus virulence factors containing the SaeR-binding domain. Data demonstrate that the pathogen response to IAV infection impacts host outcome and provides evidence that the ability of S. aureus to sense and respond to the lung environment determines severity of pneumonia.

Secondary Bacterial Pneumonia by Staphylococcus aureus Following Influenza A Infection Is SaeR/S Dependent.

 is a common Gram-positive bacteria that is a major cause of human morbidity and mortality. The SaeR/S two-component sensory system of  is important for virulence gene transcription and pathogenesis. However, the influence of SaeR phosphorylation on virulence gene transcription is not clear. To determine the importance of potential SaeR phosphorylation sites for  virulence, we generated genomic alanine substitutions at conserved aspartic acid residues in the receiver domain of the SaeR response regulator in clinically significant  pulsed-field gel electrophoresis (PFGE) type USA300. Transcriptional analysis demonstrated a dramatic reduction in the transcript abundance of various toxins, adhesins, and immunomodulatory proteins for SaeR with an aspartic acid to alanine substitution at residue 51. These findings corresponded to a significant decrease in cytotoxicity against human erythrocytes and polymorphonuclear leukocytes, the ability to block human myeloperoxidase activity, and pathogenesis during murine soft-tissue infection. Analysis of SaeR sequences from over 8,000 draft  genomes revealed that aspartic acid residue 51 is 100% conserved. Collectively, these results demonstrate that aspartic acid residue 51 of SaeR is essential for  virulence and underscore a conserved target for novel antimicrobial strategies that treat infection caused by this pathogen.

Article	Year
Secondary Bacterial Pneumonia by Staphylococcus aureus Following Influenza A Infection Is SaeR/S Dependent. The Journal of infectious diseases\| PubMed ID: 29668950	2018
Aspartic Acid Residue 51 of SaeR Is Essential for Virulence. Frontiers in microbiology\| PubMed ID: 30619166	2018

Timothy R. Borgogna

Biography

JoVE Journal Publications

Other Publications