Streptococcus pneumoniae and Staphylococcus aureus pneumonia induce distinct metabolic responses
Carolyn M Slupsky1, Andriy Cheypesh, Danny V Chao
1Department of Medicine, and Magnetic Resonance Diagnostics Centre, 550A HMRC, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Abstract:
Pneumonia is an infection of the lower respiratory tract caused by microbial pathogens. Two such pathogens, Streptococcus pneumoniae and Staphylococcus aureus, are the most common causes of community-acquired and hospital-acquired pneumonia respectively. Each expresses strains highly resistant to penicillin and other antibiotics, and a significant number of people succumb to infection by these pathogens every year. Urinary metabolite changes in a C57Bl/6 mouse model with lung infection from either S. pneumoniae or S. aureus were characterized using multivariate targeted profiling data obtained from (1)H NMR spectra. Marked changes in the urinary metabolite profile occurred within 24 h after infection with either pathogen. Specifically, significant decreases in TCA cycle intermediates, coupled with increases in fucose, creatine, and taurine were observed in the urine of S. pneumoniae-treated mice. Infection with S. aureus resulted in the decrease of a number of urinary metabolites including 1-methylnicotinamide, 3-methyl-2-oxovalerate, 2-oxoisocaproate, N-isovaleroylglycine and others. Disturbances in gut-derived microbial metabolites were also observed. Analysis of metabolic trajectory data indicated that, as the mice recovered from infection, their urinary metabolic profile became similar to that of the preinfected state. These results underline the potential of metabolomics as a tool for diagnosis, health monitoring, and drug development, and show its usefulness for understanding microbial-host interactions.
Insights
This study reveals distinct urinary metabolic changes in mice infected with Streptococcus pneumoniae or Staphylococcus aureus. Metabolomics can track pneumonia progression and recovery, aiding diagnosis and drug development.
Area of Science:
- Microbiology
- Metabolomics
- Infectious Diseases
Background:
- Pneumonia, a lower respiratory tract infection, is commonly caused by Streptococcus pneumoniae and Staphylococcus aureus.
- Antibiotic resistance in these pathogens poses a significant global health threat.
- Understanding host-pathogen interactions is crucial for developing new diagnostics and therapeutics.
Purpose of the Study:
- To characterize urinary metabolite alterations in a mouse model during pneumonia caused by S. pneumoniae and S. aureus.
- To investigate the potential of metabolomics for monitoring infection and recovery.
- To explore host-microbial metabolic interplay during pneumonia.
Main Methods:
- Utilized a C57Bl/6 mouse model infected with either S. pneumoniae or S. aureus.
- Employed multivariate targeted profiling of (1)H NMR spectra to analyze urinary metabolites.
- Tracked metabolic trajectories throughout the infection and recovery phases.
Main Results:
- Significant urinary metabolic profile changes were observed within 24 hours of infection.
- S. pneumoniae infection led to decreased TCA cycle intermediates and increased fucose, creatine, and taurine.
- S. aureus infection caused a decrease in various metabolites, including 1-methylnicotinamide and others, alongside gut-derived microbial metabolite disturbances.
Conclusions:
- Urinary metabolomics effectively captures host responses to bacterial pneumonia.
- Metabolic profiles return to baseline levels upon recovery, indicating potential for health monitoring.
- Metabolomics offers a promising avenue for pneumonia diagnosis, drug development, and understanding host-pathogen dynamics.
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