Streptococcus pneumoniae and Staphylococcus aureus Pneumonia Induce Distinct Metabolic Responses

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.

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

“…In particular, urine metabolomics is well suited for young children and in patients in whom venous access is problematic or for those who are averse to blood sampling. Notably, pathogen-specific changes in urine metabolites were detected in an experimental model of pneumonia (31). This was mimicked in the human situation, in which this approach successfully differentiated bacterial and viral pneumonias (32).…”

Metabolomics of Bronchoalveolar Lavage Differentiate Healthy HIV-1-Infected Subjects from Controls

“…Additionally, metabolomics have been used to understand metabolic changes that occur during long-term bacterial infection 11 and even to improve diagnostic capabilities of community-acquired pneumonia. [12][13][14] There is a limited amount of data regarding metabolomic approaches in HIV-1-infected patients. Small studies have been done to characterize the profile of oral wash metabolites, 15 to identify differentially regulated metabolites in cerebrospinal fluid of SIV-infected monkeys 16 and humans 17 with central nervous system disease, and to investigate drug interactions and side effects.…”

Urine Metabolite Analysis Offers Potential Early Diagnosis of Ovarian and Breast Cancers

“…We have shown that NMR spectroscopy coupled with targeted profiling techniques offers a powerful approach to generate high-density metabolic data on biofluids (3)(4)(5)(6)(7)(8). Multivariate statistical analysis, including principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA), or orthogonal partial least-squares-discriminant analysis (OPLS-DA) can be applied to these data or complex spectral data to aid in the characterization of changes related to a biological perturbation or disease.…”