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A novel extracellular vesicle-associated endodeoxyribonuclease helps
Streptococcus pneumoniae evade neutrophil extracellular traps and is required for
full virulence
#MMPMID29789571
Jhelum H
; Sori H
; Sehgal D
Sci Rep
2018[May]; 8
(1
): 7985
PMID29789571
show ga
Streptococcus pneumoniae (pneumococcus) is a major bacterial pathogen that causes
pneumonia and septicemia in humans. Pneumococci are cleared from the host
primarily by antibody dependent opsonophagocytosis by phagocytes like
neutrophils. Neutrophils release neutrophil extracellular traps (NETs) on
contacting pneumococci. NETs immobilize pneumococci and restrict its
dissemination in the host. One of the strategies utilized by pneumococci to evade
the host immune response involves use of DNase(s) to degrade NETs. We screened
the secretome of autolysin deficient S. pneumoniae to identify novel DNase(s).
Zymogram analysis revealed 3 bands indicative of DNase activity. Mass
spectrometric analysis led to the identification of TatD as a potential
extracellular DNase. Recombinant TatD showed nucleotide sequence-independent
endodeoxyribonuclease activity. TatD was associated with extracellular vesicles.
Pneumococcal secretome degraded NETs from human neutrophils. Extracellular
vesicle fraction from tatD deficient strain showed little NET degrading activity.
Recombinant TatD efficiently degraded NETs. tatD deficient pneumococci showed
lower bacterial load in lungs, blood and spleen in a murine sepsis model compared
to wildtype strain, and showed less severe lung pathology and compromised
virulence. This study provides insights into the role of a novel extracellular
DNase in evasion of the innate immune system.
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