Role of the NLRP3 Inflammasome in Escherichia Coli and Staphylococcus Aureus Bacteria

Study Overview
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Brief Summary
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Our previous studies delineate a novel pathway of immune activation in animals that the investigators have named Anti-Virulence Immunity (AVI). Using a mice model of bacteremia, the investigators have demonstrated that Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) activity is sensed by the immune system. This immune sensing results in a rapid bacterial clearing during bacteremia triggered by uropathogenic E. coli-expressing CNF1. The investigators already confirmed the involvement of one inflammasome using macrophages isolated from Knock-out mice. The investigators have recently determined the conservation in human monocytes of the interleukin -1beta maturation triggered by CNF1 and observed the heterogeneous capacity of monocytes to respond to the CNF1 treatment depending on the donors. Here, to determine the importance in natura of AVI the investigators will analyze the blood content of patients presenting E. coli and S. aureus bacteremia. The DNA of monocytes isolated from patients will be extracted and various genes implicated in the activity of various inflammasomes will be sequenced to identify mutations that could explain the susceptibility to bacteremia or a specific clinical presentation, i.e. requirement of a management in ICU because of organ failure.

Official Title
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Role of the NLRP3 Inflammasome in Escherichia Coli and Staphylococcus Aureus Bacteria

Conditions
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Escherichia Coli Infections, Staphylococcus Aureus

Intervention / Treatment
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* Genetic: Sample analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with S. aureus or E. coli bacteriostatic bacteremia defined by at least one positive blood culture bottle Patient requiring a blood test as part of his bacteremia not subject to a judicial protection measure Signature of the non-opposition of consent (for minor patients signed by one of the parents or the representative of the parental authority) Affiliation to social security Exclusion Criteria: Immunocompromised patient defined by: current immunosuppressive therapies: corticosteroids, chemotherapy, biotherapy solid organ transplant patient or hematopoietic stem cell transplant chemotherapy-induced neutropenia Congenital immune deficiency bacteremia related to a peripheral or central catheter Urinary obstruction not lifted within the first 24 hours of management Intra-abdominal infection collected undrained in the first 24 hours of management primary infectious focus represented by mechanically ventilated pneumonia Pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients presenting E. coli and S. aureus bacteremia<br>Here, to determine the importance of the mutation we will analyze the blood content of patients presenting E. coli and S. aureus bacteremia | Genetic: Sample analysis<br>* Here, to determine the importance of the mutation we will analyze the blood content of patients presenting E. coli and S. aureus bacteremia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish an association between mutations in some inflammasomes and occurrence of E. coli associated with sepsis. |  | 1 hour | 
| Establish an association between mutations in some inflammasomes and occurrence of S. aureus bacteremia associated with sepsis. |  | 1 hour |