Proteomics

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Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

ABSTRACT: Neutrophils have an important role in rapid antimicrobial defenses against and resolution of urinary tract infections (UTIs). We show that a mechanism known as neutrophil extracellular trap (NET) formation is a strategy to combat pathogens in the urinary tract. Viscous aggregates that were present in human urine sediments revealed high extracellular DNA content. The DNA formed a scaffold to which antimicrobial effector proteins derived from different neutrophil subcellular compartments bound. Treatment with deoxyribonuclease I solubilized these structures. We observed massive proteolytic degradation in the NETs with apparently dominant roles for the neutrophil granule proteases elastase, proteinase 3, and cathepsin G. In a UTI case with Staphylococcus aureus as the infectious agent, high abundance of autolysins and immune evasion factors in a cell-free NET extract suggested that controlled cell wall autolysis plays a role in derailing the host immune response and allows some bacterial cells to survive following entrapment in NETs.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

SUBMITTER: Yanbao Yu  

LAB HEAD: Yanbao Yu

PROVIDER: PXD005688 | Pride | 2017-01-23

REPOSITORIES: Pride

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Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections.

Yu Yanbao Y   Kwon Keehwan K   Tsitrin Tamara T   Bekele Shiferaw S   Sikorski Patricia P   Nelson Karen E KE   Pieper Rembert R  

PLoS pathogens 20170127 1

Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, rel  ...[more]

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