The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions

Mavromatis, C; Bokil, NJ; Totsika, M; Kakkanat, A; Schaale, K; Cannistraci, CV; Ryu, T; Beatson, SA; Ulett, GC; Schembri, MA; Sweet, MJ; Ravasi, T

The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions

Mavromatis, C Bokil, NJ

Totsika, M Kakkanat, A Schaale, K Cannistraci, CV Ryu, T Beatson, SA

Ulett, GC Schembri, MA Sweet, MJ Ravasi, T

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Publication Type:: Journal Article
Citation:: Cellular Microbiology, 2015, 17 (5), pp. 730 - 746
Issue Date:: 2015-05-01

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Field	Value	Language
dc.contributor.author	Mavromatis, C	en_US
dc.contributor.author	Bokil, NJ https://orcid.org/0000-0003-3202-9249	en_US
dc.contributor.author	Totsika, M	en_US
dc.contributor.author	Kakkanat, A	en_US
dc.contributor.author	Schaale, K	en_US
dc.contributor.author	Cannistraci, CV	en_US
dc.contributor.author	Ryu, T	en_US
dc.contributor.author	Beatson, SA https://orcid.org/0000-0002-1806-3283	en_US
dc.contributor.author	Ulett, GC	en_US
dc.contributor.author	Schembri, MA	en_US
dc.contributor.author	Sweet, MJ	en_US
dc.contributor.author	Ravasi, T	en_US
dc.date.available	2014-11-11	en_US
dc.date.issued	2015-05-01	en_US
dc.identifier.citation	Cellular Microbiology, 2015, 17 (5), pp. 730 - 746	en_US
dc.identifier.issn	1462-5814	en_US
dc.identifier.uri	http://hdl.handle.net/10453/75060
dc.description.abstract	© 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. 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 24h 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 24h 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.	en_US
dc.relation.ispartof	Cellular Microbiology	en_US
dc.relation.isbasedon	10.1111/cmi.12397	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Macrophages	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Escherichia coli	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Sequence Analysis, RNA	en_US
dc.subject.mesh	Host-Pathogen Interactions	en_US
dc.title	The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.citation.volume	17	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1108 Medical Microbiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	17	en_US

Abstract:

© 2014 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. 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 24h 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 24h 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.

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http://hdl.handle.net/10453/75060