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ABSTRACT: Escherichia coli ST38 isolates from human patients with urinary tract infections.

PROVIDER: PRJEB52832 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR9726640_1.fastq.gz	Fastqsanger.gz
	ERR9726640_2.fastq.gz	Fastqsanger.gz
	ERR9726631_1.fastq.gz	Fastqsanger.gz
	ERR9726631_2.fastq.gz	Fastqsanger.gz
	ERR9726641_1.fastq.gz	Fastqsanger.gz

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Project description:Urinary tract infections (UTIs) constitute a highly relevant model of microbial adaptation, in which the contrasting effects of pathogens and commensals on host tissues are clearly displayed. While virulent Escherichia coli cause severe, potentially life-threatening disease by breaking the inertia of the mucosal barrier and infecting the kidneys, the most common outcome of bacteriuria is an asymptomatic carrier state resembling commensalism at other mucosal sites. It remains unclear if the lack of destructive inflammation merely reflects low virulence or if carrier strains actively inhibit disease associated responses in the host. To address this question, we examined the effects of asymptomatic bacterial carriage on host gene expression. Therapeutic urinary tract inoculation with the prototype ABU strain E. coli 83972 is a safe alternative approach in patients with therapy-resistant recurrent UTI. The strain establishes persistent bacteriuria, protecting patients against super-infection with more virulent strains. Using this protocol, we examined if the establishment of asymptomatic bacterial carriage alters host gene expression. After antibiotic treatment to remove prior infection, patients were inoculated with E. coli 83972 through a catheter. Blood samples were obtained before and 24 h after inoculation.

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Project description:Escherichia coli is an important human pathogen, among others a cause of severe diarrhea diseases and urinary tract infections. The ability to distinguish different pathogenic E. coli subspecies is crucial for correct treatment of the infection. Characterization and quantification of clinical isolates proteomes can provide details of the organisms’ metabolism and specific virulence factors. We performed a systematic quantitative proteomic analysis on a representative selection of 16 pathogenic and 2 commensal E. coli strains, together with 5 pathogenic Shigella strains. The analysis yielded a dataset of more than 4 thousand proteins, with an average of 2 thousand proteins per strain and 980 proteins common to all strains. Statistical comparison of label-free quantitative levels of 750 proteins, which were quantified in all strains, revealed that levels of a majority of the shared proteins vary substantially among specific strains. Theses quantitative protein profiles clearly distinguished E. coli strains from Shigella and largely separated commensal E. coli strains from intestinal and extraintestinal E. coli isolates.

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Project description:Urinary tract infections (UTIs) are a very common bacterial infectious disease in humans, and uropathogenic Escherichia coli (UPEC) are the most frequent cause of UTIs. During infection, UPEC must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrated that the small RNA (sRNA) RyfA of UPEC strains was required for resistance to oxidative and osmotic stresses. Inactivation of ryfA in UPEC strain CFT073 decreased urinary tract colonization in CBA/J mice and the ryfA mutant also had reduced production of type 1 and P fimbriae, which are known to be important for UTI. Transcriptomic analysis of the ryfA mutant showed changes in expression of genes associated with general stress responses, metabolism, biofilm formation and genes coding for cell surface proteins. Furthermore, loss of ryfA also reduced UPEC survival in human macrophages. Thus, ryfA plays a key regulatory role in UPEC adaptation to stress, that contributes to UTI and survival in macrophages.

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