An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps.
Streptococcus pneumoniae (pneumococcus) is the most common cause of community-acquired pneumonia, with high morbidity and mortality worldwide. A major feature of pneumococcal pneumonia is an abundant neutrophil infiltration . It was recently shown that activated neutrophils release neutrophil extracellular traps (NETs), which contain antimicrobial proteins bound to a DNA scaffold. NETs provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes extracellularly. Here, we show that pneumococci are trapped but, unlike many other pathogens, not killed by NETs. NET trapping in the lungs, however, may allow the host to confine the infection, reducing the likelihood for the pathogen to spread into the bloodstream. DNases are expressed by many Gram-positive bacterial pathogens, but their role in virulence is not clear. Expression of a surface endonuclease encoded by endA is a common feature of many pneumococcal strains. We show that EndA allows pneumococci to degrade the DNA scaffold of NETs and escape. Furthermore, we demonstrate that escaping NETs promotes spreading of pneumococci from the upper airways to the lungs and from the lungs into the bloodstream during pneumonia.
Beiter
Katharina
K
Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna SE-171 82, Sweden.
Wartha
Florian
F
Albiger
Barbara
B
Normark
Staffan
S
Zychlinsky
Arturo
A
Henriques-Normark
Birgitta
B
D000818:Animals; D002417:Cattle; D017714:Community-Acquired Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D004247:DNA / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism*; D005110:Extracellular Space; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000472:pathogenicity
D004247:DNA; D004720:Endonucleases