Neutrophil Extracellular Traps (NETs) Mediated Killing of Carbapenem-resistant Pseudomonas Aeruginosa.

NCT ID: NCT06441708

Last Updated: 2024-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-06-01

Study Completion Date

2025-07-01

Brief Summary

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Aim of the work:

To determine the killing ability of neutrophils to ATCC 27853, carbapenem-resistant P. aeruginosa.

To compare between the ability of ATCC 27853, carbapenem-resistant P. aeruginosa to induce NETs formation.

To quantify NETS formation in response to PMA, ATCC 27853, carbapenem-resistant P. aeruginosa using immunofluorescence.

To determine the killing ability of NETs on ATCC 27853, carbapenem-resistant P. aeruginosa.

Detailed Description

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Pseudomonas aeruginosa is one of the most common pathogens in healthcare-associated infections worldwide, causing ventilator-associated pneumonia, urinary tract infections in patients with long-term urinary catheterization, wound infections, bloodstream infections, and otitis (reynolds and kollef, 2021).

Carbapenem-resistant-P. aeruginosa infection is a prominent disease connected to healthcare due to multiple mechanisms, such as target alteration, active efflux, decreased permeability, and enzyme degradation (Tenover et al., 2022).

Neutrophils are the most prominent cellular component of the innate immune response and are essential for defense against bacterial infections (Chapple et al., 2023).

In addition to traditional antimicrobial processes of neutrophils, a unique web-like structure, is termed neutrophil extracellular traps (NETs), formed and released by highly active neutrophils. NETs consist of extracellular deoxyribonucleic acid (eDNA) filaments coated with histones and neutrophil granule proteins such as Myeloperoxidase (MPO), neutrophil elastase (NE), lactoferrin, cathepsins, calprotectin, LL-37, and defensin (Papayannopoulos, 2018).

MPO and NE are key components of NETs and play roles in their function and structure. MPO, a heme protein primarily stored in the granules of neutrophils, contributes significantly to microbial killing within NETs. It catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride ions, a reaction central to the antimicrobial properties of NETs. NE, another granule protein extends to modulating inflammation and immune response (Islam et al., 2023).

The role of NETs during bacterial infection is not completely clear. It promoted the clearance of bacteria by facilitating the entrapping and killing of these pathogens, However, it has been described that the granular proteins released within the NETs act mainly as a regulator of inflammation due to the action on different cytokines, rather than as a bactericidal mechanism (Clancy, 2018).

P. aeruginosa-mediated factors contribute to the NETosis and release of a large amount of NETs. However, sequestration of P. aeruginosa by traps does not lead to the complete destruction of bacteria, but, it promotes their microcolonization, aggregation, and finally biofilm formation, leading to the formation of higher resistance to NETs-mediated bactericidal activity (Rahman and Gadjeva, 2014).

Neutrophils formed a NET-barrier to keep bacteria outside in the form of biofilm and prevent their spread to the brain. Thus, the NET formation is probably a useful mechanism for protecting the brain against infections through the ocular route (Thanabalasuriar et al., 2019).

Conditions

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Neutrophil Extracellular Traps Formation

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Interventions

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No intervention

No intervention on patient

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* isolates will be isolated from different clinical samples including wound respiratory tract urine and blood. \_carbapenem-resistant P. aeruginosa isolates.

Exclusion Criteria

* \_carbapenem-sensitive P. aeruginosa isolates.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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NSHussein

Assistant Lecturer at medical Microbilogy and Immunology department

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

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Noura Samir Hussein, Assistant lecturer

Role: CONTACT

00201002606302

Other Identifiers

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Pseudomonas aeruginosa

Identifier Type: -

Identifier Source: org_study_id

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