Transformation of nonencapsulated Streptococcus pneumoniae during systemic infection

Streptococcus pneumoniae (pneumococcus) is a principal cause of bacterial middle ear infections, pneumonia, and meningitis. Capsule-targeted pneumococcal vaccines have likely contributed to increased carriage of nonencapsulated S. pneumoniae (NESp). Some NESp lineages are associated with highly efficient DNA uptake and transformation frequencies. However, NESp strains lack capsule that may increase disease severity. We tested the hypothesis that NESp could acquire capsule during systemic infection and transform into more virulent pneumococci. We reveal that NESp strains MNZ67 and MNZ41 are highly transformable and resistant to multiple antibiotics. Natural transformation of NESp when co-administered with heat-killed encapsulated strain WU2 in a murine model of systemic infection resulted in encapsulation of NESp and increased virulence during bacteremia. Functional capsule production increased the pathogenic potential of MNZ67 by significantly decreasing complement deposition on the bacterial surface. However, capsule acquisition did not further decrease complement deposition on the relatively highly pathogenic strain MNZ41. Whole genome sequencing of select transformants demonstrated that recombination of up to 56.7 kbp length occurred at the capsule locus, along with additional recombination occurring at distal sites harboring virulence-associated genes. These findings indicate NESp can compensate for lack of capsule production and rapidly evolve into more virulent strains.