Capsule genetics in Streptococcus pneumoniae and a possible role for transposition in the generation of the type 3 locus

The capsule genes of Streptococcus pneumoniae have a cassette-like organiza tion in which the type-specific biosynthetic genes are flanked by genes sha red among the different capsular serotypes, This general organization has b een identified in the capsule loci of all serotypes analyzed to date, but s ignificant differences that may help explain novel capsule type formation a re beginning tot emerge. In particular, analysis of the type 3 locus has re vealed its most striking feature to be a preponderance of partial genes tha t have homology to sequences involved in polysaccharide biosynthesis and tr ansposition. The predicted proteins of cps3M, the most downstream type 3-sp ecific gene, and tnpA and plpA, the non-type-specific flanking sequences do wnstream of cps3M, have homologies with phosphomutases, transposases, and p eptide permeases, respectively. All three of these sequences are truncated when compared to their respective homologs, Mutation and transcription anal yses of these partial sequences showed that none of these sequences is esse ntial for type 3 polysaccharide synthesis but that all are transcribed. Par tial sequences were also identified in the region upstream of the type 3-sp ecific genes. The type 3 locus structure is conserved among independent typ e 3 isolates but similar deletions are not apparent in the common, non-type -specific flanking sequences in other capsular types. A role for transposit ion-mediated events in the generation of the type 3 locus, and possibly oth er pneumococcal capsule loci, is suggested by these findings.