Ignite Creation Date:
2024-06-16 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06441708
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-04
First Post:
2024-05-29
Brief Title:
Neutrophil Extracellular Traps NETs Mediated Killing of Carbapenem-resistant Pseudomonas Aeruginosa
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Neutrophil Extracellular Traps NETs Mediated Killing of Carbapenem-resistant Pseudomonas Aeruginosa Isolated From Hospital Acquired Infections in Assiut University Hospitals
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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:
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None