In Vivo Capsular Switch in Streptococcus pneumoniae – Analysis by Whole Genome Sequencing

摘要: Two multidrug resistant strains of Streptococcus pneumoniae – SV35-T23 (capsular type 23F) and SV36-T3 3) were recovered from the nasopharynx two adult patients during an outbreak pneumococcal disease in a New York hospital 1996. Both belonged to pandemic lineage PMEN1 but they differed strikingly virulence when tested mouse model IP infection: as few 1000 CFU SV36 killed all mice within 24 hours after inoculation while was avirulent. Whole genome sequencing (WGS) isolates performed (i) test if these belonging same clonal identical epidemiological scenario only their capsular genes? (ii) vast difference between mostly or exclusively due III capsule. WGS demonstrated extensive differences including over 2500 single nucleotide polymorphisms core genes also 36 genetic determinants: 25 which unique 11 strain SV36-T3. Nineteen 9 bacteriocin genes. Using transformation laboratory, region replaced by 3 generate recombinant SV35-T3* virulent parental SV36-T3* murine capsule major factor chinchilla well. On other hand, careful comparison laboratory constructed suggested that some additional determinants present not may contribute progression middle ear disease. The nature this remains be identified.