title: Adaptation of Listeria monocytogenes to oxidative and nitrosative stress in IFN-γ-activated macrophages.
abstract: IFN-γ-activated macrophages are considered to be the primary effector cells in host defense against Listeria monocytogenes infections. However despite the induction of the complex host defense mechanisms, survival of L. monocytogenes in activated macrophages is still observed. Here we used a whole genome-based transcriptome approach to examine for bacterial genes specifically induced in IFN-γ-activated macrophages. We demonstrated that cells activated by IFN-γ had elevated oxidative and nitrosative stress levels in both the activated macrophages as well as in the intracellular replicating bacteria isolated from these infected cells. We found that a subset of 21 transcripts were specifically differentially regulated in bacteria growing in cells pretreated with IFN-γ. Bioinformatics and functional analysis revealed that many of these genes have roles involved in overcoming oxidative stress and contribute to bacterial survival within activated macrophages. We detected increased transcription of the putative trpE gene of L. monocytogenes, encoding an anthranilate synthase, in bacteria growing in IFN-γ cells indicating host cell metabolic restriction of bacterial growth. Indeed we found enhanced activation of host cell genes involved in the kynurenine pathway indicating an increased need of L. monocytogenes for tryptophan during replication in IFN-γ-activated macrophages.
authors.affiliation: Institute for Medical Microbiology, Justus-Liebig-University, Giessen, Germany. Mobarak.Mraheil@mikrobio.med.uni-giessen.de
authors.forename: Mobarak Abu
authors.initials: MA
authors.lastname: Mraheil
authors.forename: André
authors.initials: A
authors.lastname: Billion
authors.forename: Walid
authors.initials: W
authors.lastname: Mohamed
authors.forename: Deepak
authors.initials: D
authors.lastname: Rawool
authors.forename: Torsten
authors.initials: T
authors.lastname: Hain
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
mesh_terms: D000222:Adaptation, Physiological; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D007371:Interferon-gamma / Q000276:immunology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D046228:Microarray Analysis; D050296:Microbial Viability; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000633:toxicity; D013312:Stress, Physiological
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D007371:Interferon-gamma