A Single Gene (tts) Located outside the cap Locus Directs the Formation of Streptococcus pneumoniae Type 37 Capsular Polysaccharide

Abstract

The molecular aspects of the type 37 pneumococcal capsular biosynthesis, a homopolysaccharide composed of sophorosyl units (β-d-Glc-(1→2)-β-d-Glc) linked by β-1,3 bonds, have been studied. Remarkably, the biosynthesis of the type 37 capsule is driven by a single gene (tts) located far apart from the cap locus responsible for capsular formation in all of the types characterized to date in Streptococcus pneumoniae. However, a cap37 locus virtually identical to the cap33f cluster has been found in type 37 strains, although some of its genes are inactivated by mutations. The tts gene has been sequenced and its transcription start point determined. Tts shows sequence motifs characteristic of cellulose synthases and other β-glycosyltransferases. Insertion of the tts gene into the pneumococcal DNA causes a noticeable genome reorganization in such a way that genes normally separated by more than 350 kb in the chromosome are located together in clinical isolates of type 37. Encapsulated pneumococcal strains belonging to 10 different serotypes (or serogroups) transformed with tts synthesized type 37 polysaccharide, leading to the formation of strains that display the binary type of capsule. Type 37 pneumococcus constitutes the first case of a natural, genetically binary strain and represents a novel alternative to the mechanisms of intertype transformation.