651. Non-encapsulation of Pneumococci as a Potential Evasion Mechanism From Vaccines

Abstract

BackgroundOur group has been continuously performing epidemiological analyses on capsular types of pneumococci since 2007. Pneumococcal conjugate vaccine decreased the proportion of nonvaccine capsular types. Furthermore, null-capsule isolates that produced PspK were also identified in our analysis. In this study, we analyzed the genetic background of null-capsule pneumococci and the mechanism of nonencapsulation.MethodsTwenty-seven null-capsule isolates from 430 pneumococci that were isolated between 2010 and 2014 were used for this study. The capsular type was identified by DNA sequence-based methods, and genetic backgrounds were compared by multilocus sequence typing. Among the null-capsule isolates, the SP2852 strain was employed for non-encapsulation analysis. The pspK gene of this strain was replaced with ermB by homologous recombination (SP2852 ΔpspK::ermB). Then, genomic DNA from SP2852 ΔpspK::ermB was transformed into encapsulated isolates via natural transformation. Clindamycin-resistant isolates were further analyzed by sequence.ResultsThe proportion of null-capsule isolates tended to increase from 5% in 2010–2011 to 12.3% in 2014. These null-capsule isolates were classified into 14 STs that included STs previously identified as capsule-positive isolates. To assess non-encapsulation via natural transformation, two encapsulated strains (serotype 19F and 14) were cultured with genomic DNA from SP2852 ΔpspK::ermB. Subsequently, clindamycin-resistant null-capsule isolates were detected with high frequency (2.5 × 10–4–8.7 × 10–5). Sequence analysis showed capsular coding regions of these null-capsule isolates were replaced with that of ΔpspK::ermB. Furthermore, these isolates grew significant faster than their parent strains.ConclusionNull-capsule isolates with various genetic backgrounds were revealed gradually after introduction of vaccine. Moreover, encapsulated strains could take up genomic DNA of null-capsule isolates more easily and become a null-capsule strain by homologous recombination, suggesting that non-encapsulation and acquiring PspK resulted in the emergence of null-capsule strains by natural transformation. Furthermore, non-encapsulation could be beneficial for pneumococci as an evasion mechanism from vaccines.Disclosures All authors: No reported disclosures.