Open AccessThe co‐transcriptome of uropathogenic E scherichia coli ‐infected mouse macrophages reveals new insights into host–pathogen interactions
Author(s) -
Mavromatis Charalampos Harris,
Bokil Nilesh J.,
Totsika Makrina,
Kakkanat Asha,
Schaale Kolja,
Cannistraci Carlo V.,
Ryu Taewoo,
Beatson Scott A.,
Ulett Glen C.,
Schembri Mark A.,
Sweet Matthew J.,
Ravasi Timothy
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12397
Subject(s) - biology , transcriptome , microbiology and biotechnology , pathogen , gene , escherichia coli , multiplicity of infection , bacteria , phenotype , host (biology) , gene expression , genetics
Summary Urinary tract infections ( UTI ) are among the most common infections in humans. Uropathogenic E scherichia 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: UTI 89, 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 UTI 89 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 UTI 89 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.