title: The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions.
abstract: Urinary tract infections (UTI) are among the most common infections in humans. Uropathogenic Escherichia coli (UPEC) can invade and replicate within bladder epithelial cells, and some UPEC strains can also survive within macrophages. To understand the UPEC transcriptional programme associated with intramacrophage survival, we performed host-pathogen co-transcriptome analyses using RNA sequencing. Mouse bone marrow-derived macrophages (BMMs) were challenged over a 24 h time course with two UPEC reference strains that possess contrasting intramacrophage phenotypes: UTI89, which survives in BMMs, and 83972, which is killed by BMMs. Neither of these strains caused significant BMM cell death at the low multiplicity of infection that was used in this study. We developed an effective computational framework that simultaneously separated, annotated and quantified the mammalian and bacterial transcriptomes. Bone marrow-derived macrophages responded to the two UPEC strains with a broadly similar gene expression programme. In contrast, the transcriptional responses of the UPEC strains diverged markedly from each other. We identified UTI89 genes up-regulated at 24 h post-infection, and hypothesized that some may contribute to intramacrophage survival. Indeed, we showed that deletion of one such gene (pspA) significantly reduced UTI89 survival within BMMs. Our study provides a technological framework for simultaneously capturing global changes at the transcriptional level in co-cultures, and has generated new insights into the mechanisms that UPEC use to persist within the intramacrophage environment.
authors.affiliation: Division of Biological and Environmental Sciences and Engineering, Division of Computer, Electrical and Mathematical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia; Division of Medical Genetics, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, USA.
authors.forename: Charalampos Harris
authors.initials: CH
authors.lastname: Mavromatis
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Bokil
authors.forename: Makrina
authors.initials: M
authors.lastname: Totsika
authors.forename: Asha
authors.initials: A
authors.lastname: Kakkanat
authors.forename: Kolja
authors.initials: K
authors.lastname: Schaale
authors.forename: Carlo V
authors.initials: CV
authors.lastname: Cannistraci
authors.forename: Taewoo
authors.initials: T
authors.lastname: Ryu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.forename: Glen C
authors.initials: GC
authors.lastname: Ulett
authors.forename: Mark A
authors.initials: MA
authors.lastname: Schembri
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sweet
authors.forename: Timothy
authors.initials: T
authors.lastname: Ravasi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology* / Q000502:physiology*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D017423:Sequence Analysis, RNA