l-Proline protects mice challenged by Klebsiella pneumoniae bacteremia.

Abstract

OBJECTIVE: K. pneumoniae, a common pathogen that frequently causes bacteremia in clinic, is unresponsive to most of known antibiotics, thus cumulatively exacerbating empirical therapy failures. Effective strategies to control Klebsiella pneumoniae bacteremia are in high demand. One possibility is to mobilize host defense mechanisms against bacterial pathogens. METHODS: We employed GC/MS-based metabolomics to identify the changes of metabolism in mice challenged by K. pneumoniae (ATCC 43816) bacteremia. RESULTS: Compared with the mice that compromised from K. pneumoniae bacteremia, mice that survived from infection displayed the varied metabolomic profile. The differential analysis of metabolome showed that Ethanedioic acid, d-Glucose, l-Glutamine, Myo-inositol, and l-Proline were more likely associated with the host surviving a K. pneumoniae bacteremia. Further pathway enrichment analysis proposed that arginine and proline metabolism involved in outcome of K. pneumoniae bacteremia. The follow-up data showed that exogenous l-Proline but not d-Proline could decline the loads of Klebsiella pneumonia in infected blood and tissues (lung, liver and spleen) and increase the mouse survival. CONCLUSION: Our study provides an exercisable strategy of identifying metabolic biomarkers from surviving host and highlights the possibility of utilizing the metabolic biomarker as a therapy for K. pneumoniae bacteremia.