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DNA Is an Antimicrobial Component of Neutrophil Extracellular Traps


Comprising the first line of the innate immune response, neutrophils combat infectious microorganisms through the release of toxic molecules, phagocytosis of invaders and the production of the recently characterized neutrophil extracellular traps (NETs). The antimicrobial activity of NETs has been attributed to proteins bound to the DNA backbone. Our results demonstrate that the DNA lattice of each NET is potently antibacterial and elicits upregulation of protective surface modifications by the opportunistic bacterial pathogen Pseudomonas aeruginosa. These modifications, previously shown to protect bacteria from antimicrobial peptides, confer greater bacterial tolerance to DNA and NET-mediated antibacterial activity. Treatments that quench the cation chelating capacity of DNA restore bacterial viability and suppress the expression of surface modifications even in the presence of intact NETs. These observations highlight the dual function of DNA as an antibacterial component of NETs, but also a signal perceived by bacteria to induce broad host resistance strategies. Therefore, the ability of P. aeruginosa to sense and defend against the antibacterial activity of neutrophil extracellular traps may contribute to long-term survival in chronic infection sites including the Cystic Fibrosis lung.


Vyšlo v časopise: DNA Is an Antimicrobial Component of Neutrophil Extracellular Traps. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004593
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004593

Souhrn

Comprising the first line of the innate immune response, neutrophils combat infectious microorganisms through the release of toxic molecules, phagocytosis of invaders and the production of the recently characterized neutrophil extracellular traps (NETs). The antimicrobial activity of NETs has been attributed to proteins bound to the DNA backbone. Our results demonstrate that the DNA lattice of each NET is potently antibacterial and elicits upregulation of protective surface modifications by the opportunistic bacterial pathogen Pseudomonas aeruginosa. These modifications, previously shown to protect bacteria from antimicrobial peptides, confer greater bacterial tolerance to DNA and NET-mediated antibacterial activity. Treatments that quench the cation chelating capacity of DNA restore bacterial viability and suppress the expression of surface modifications even in the presence of intact NETs. These observations highlight the dual function of DNA as an antibacterial component of NETs, but also a signal perceived by bacteria to induce broad host resistance strategies. Therefore, the ability of P. aeruginosa to sense and defend against the antibacterial activity of neutrophil extracellular traps may contribute to long-term survival in chronic infection sites including the Cystic Fibrosis lung.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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