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Listeriosis downregulates hepatic cytochrome P450 enzymes in sublethal murine infection
Author(s) -
Kummer Anne,
Nishanth Gopala,
Koschel Josephin,
Klawonn Frank,
Schlüter Dirk,
Jänsch Lothar
Publication year - 2016
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201600030
Subject(s) - proteome , biology , flow cytometry , immune system , listeria monocytogenes , proteomics , cytochrome p450 , drug , enzyme , immunology , pharmacology , bioinformatics , biochemistry , bacteria , genetics , gene
Purpose Listeria monocytogenes (Lm) can cross the intestinal barrier in humans and then disseminates into different organs. Invasion of the liver occurs even in sublethal infections, however, knowledge of affected physiological processes is scarce. This study employed a sublethal murine infection model to investigate liver responses systematically by proteomics. Experimental design Liver samples from three stages of the sublethal infection covering the initial invasion, the peak of infection, and the clearance phase (1, 3, 9 days postinoculation) were analyzed in comparison to samples from noninfected mice. Apart from flow cytometry and RT‐PCRs for immune status control, liver responses were analyzed by quantitative peptide sequencing (HPLC‐Orbitrap Fusion) using 4‐plex iTRAQ‐labeling. Results Accurate MS characterized about 3600 proteins and statistics revealed 15% of the hepatic proteome as regulated. Immunological data as well as protein regulation dynamics strongly indicate stage‐specific hepatic responses in sublethal infections. Most notably, this study detected a comprehensive deregulation of drug metabolizing enzymes at all stages, including 25 components of the cytochrome P450 system. Conclusions and clinical relevance Sublethal Lm infection deregulates hepatic drug metabolizing pathways. This finding indicates the need to monitor drug administration along Lm infections, especially in all patients needing constant medication.