title: Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae against neutrophil extracellular traps.
abstract: Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococci can counteract the action of neutrophils with an antiphagocytic capsule and through electrochemical repulsion of antimicrobial peptides via addition of positive charge to the surface. Pneumococci are captured, but not killed in neutrophil extracellular traps (NETs). Here, we study the role of the polysaccharide capsule and lipoteichoic acid (LTA) modification on pneumococcal interaction with NETs. Expression of capsule (serotypes 1, 2, 4 and 9V) significantly reduced trapping by NETs, but was not required for resistance to NET-mediated killing. Pneumococci contain a dlt operon that mediates the incorporation of d-alanine residues into LTAs, thereby introducing positive charge. Genetic inactivation of dltA in non-encapsulated pneumococci rendered the organism sensitive to killing by antimicrobial components present in NETs. However, the encapsulated dltA mutant remained resistant to NET-mediated killing in vitro. Nevertheless, in a murine model of pneumococcal pneumonia, the encapsulated dltA-mutant strain was outcompeted by the wild-type upon invasion into the lungs and bloodstream. This suggests a non-redundant role for LTA alanylation in pneumococcal virulence at the early stage of invasive disease when capsule expression has been shown to be low.
authors.affiliation: Department of Bacteriology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
authors.forename: Florian
authors.initials: F
authors.lastname: Wartha
authors.forename: Katharina
authors.initials: K
authors.lastname: Beiter
authors.forename: Barbara
authors.initials: B
authors.lastname: Albiger
authors.forename: Jenny
authors.initials: J
authors.lastname: Fernebro
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
authors.forename: Staffan
authors.initials: S
authors.lastname: Normark
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry / Q000276:immunology*; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D009876:Operon / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013682:Teichoic Acids / Q000737:chemistry / Q000276:immunology*; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D013682:Teichoic Acids; D037521:Virulence Factors; C009900:lipoteichoic acid; D000409:Alanine