title: A point mutation in cpsE renders Streptococcus pneumoniae nonencapsulated and enhances its growth, adherence and competence.
abstract: BACKGROUND
  The polysaccharide capsule is a major virulence factor of the important human pathogen Streptococcus pneumoniae. However, S. pneumoniae strains lacking capsule do occur.
  
  
  RESULTS
  Here, we report a nasopharyngeal isolate of Streptococcus pneumoniae composed of a mixture of two phenotypes; one encapsulated (serotype 18C) and the other nonencapsulated, determined by serotyping, electron microscopy and fluorescence isothiocyanate dextran exclusion assay.By whole genome sequencing, we demonstrated that the phenotypes differ by a single nucleotide base pair in capsular gene cpsE (C to G change at gene position 1135) predicted to result in amino acid change from arginine to glycine at position 379, located in the cytoplasmic, enzymatically active, region of this transmembrane protein. This SNP is responsible for loss of capsule production as the phenotype is transferred with the capsule operon. The nonencapsulated variant is superior in growth in vitro and is also 117-fold more adherent to and more invasive into Detroit 562 human epithelial cells than the encapsulated variant.Expression of six competence pathway genes and one competence-associated gene was 11 to 34-fold higher in the nonencapsulated variant than the encapsulated and transformation frequency was 3.7-fold greater.
  
  
  CONCLUSIONS
  We identified a new single point mutation in capsule gene cpsE of a clinical S. pneumoniae serotype 18C isolate sufficient to cause loss of capsule expression resulting in the co-existence of the encapsulated and nonencapsulated phenotype. The mutation caused phenotypic changes in growth, adherence to epithelial cells and transformability. Mutation in capsule gene cpsE may be a way for S. pneumoniae to lose its capsule and increase its colonization potential.
authors.forename: Thierry O
authors.initials: TO
authors.lastname: Schaffner
authors.forename: Jason
authors.initials: J
authors.lastname: Hinds
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Gould
authors.forename: Daniel
authors.initials: D
authors.lastname: Wüthrich
authors.forename: Rémy
authors.initials: R
authors.lastname: Bruggmann
authors.forename: Marianne
authors.initials: M
authors.lastname: Küffer
authors.forename: Kathrin
authors.initials: K
authors.lastname: Mühlemann
authors.forename: Markus
authors.initials: M
authors.lastname: Hilty
authors.affiliation: Institute for Infectious Diseases, University of Bern, Friedbühlstrasse 51, Bern, CH-3010, Switzerland. lucy.hathaway@ifik.unibe.ch.
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Hathaway
mesh_terms: D001422:Bacterial Adhesion; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004252:DNA Mutational Analysis; D061269:DNA Transformation Competence; D004847:Epithelial Cells / Q000382:microbiology; D016680:Genome, Bacterial; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000382:microbiology; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification / Q000502:physiology*; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; D050505:Mutant Proteins