title: Streptococcus pneumoniae arginine synthesis genes promote growth and virulence in pneumococcal meningitis.
abstract: Streptococcus pneumoniae (pneumococcus) is a major human pathogen causing pneumonia, sepsis and bacterial meningitis. Using a clinical phenotype based approach with bacterial whole-genome sequencing we identified pneumococcal arginine biosynthesis genes to be associated with outcome in patients with pneumococcal meningitis. Pneumococci harboring these genes show increased growth in human blood and cerebrospinal fluid (CSF). Mouse models of meningitis and pneumonia showed that pneumococcal strains without arginine biosynthesis genes were attenuated in growth or cleared, from lung, blood and CSF. Thus, S. pneumoniae arginine synthesis genes promote growth and virulence in invasive pneumococcal disease.
authors: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, P.O. Box 22660, Amsterdam 1100 DD, the Netherlands.
authors: Jurgen R
authors: JR
authors: Piet
authors: Madelijn
authors: M
authors: Geldhoff
authors: Barbera D C
authors: BD
authors: van Schaik
authors: Matthijs C
authors: MC
authors: Brouwer
authors: Mercedes
authors: M
authors: Valls Seron
authors: Marja E
authors: ME
authors: Jakobs
authors: Kim
authors: K
authors: Schipper
authors: Yvonne
authors: Y
authors: Pannekoek
authors: Aeilko H
authors: AH
authors: Zwinderman
authors: Tom
authors: T
authors: van der Poll
authors: Antoine H C
authors: AH
authors: van Kampen
authors: Frank
authors: F
authors: Baas
authors: Arie
authors: A
authors: van der Ende
authors: Diederik
authors: D
authors: van de Beek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001120:Arginine / Q000096:biosynthesis*; D015331:Cohort Studies; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016680:Genome, Bacterial; D006801:Humans; D008297:Male; D008586:Meningitis, Pneumococcal / Q000382:microbiology*; D051379:Mice; D008875:Middle Aged; D011018:Pneumonia, Pneumococcal / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001120:Arginine
keywords: Streptococcus pneumoniae; arginine synthesis; bacterial meningitis; virulence; whole genome sequencing