Identification and genetic engineering of pneumococcal capsule-like polysaccharides in commensal oral streptococci.

UNLABELLED

Capsular polysaccharides (CPS) in are pivotal for bacterial virulence and present extensive diversity. While oral streptococci show pronounced antigenicity toward pneumococcal capsule-specific sera, insights into evolution of capsule diversity remain limited. This study reports a pneumococcal CPS-like genetic locus in , a predominant oral . The discovered locus comprises 15 genes, mirroring high similarity to those from the Wzy-dependent CPS locus of . Notably, elicited a reaction with pneumococcal 19B antiserum. Through nuclear magnetic resonance analysis, we ascertained that its CPS structure matches the chemical composition of the pneumococcal 19B capsule. By introducing the glucosyltransferase gene from a pneumococcal serotype 19C, we successfully transformed antigenicity from 19B to 19C. Furthermore, substituting serotype-specific genes, and , with their counterparts from pneumococcal serotype 19A and 19F enabled to generate 19A- and 19F-specific CPS, respectively. These findings underscore that harbors a versatile 19B-like CPS adaptable to other serotypes. Remarkably, after deleting the locus's initial gene, , responsible for sugar transfer, we noted halted CPS production, elongated bacterial chains, and diminished biofilm formation. A similar phenotype emerged with the removal of the distinct gene , which encodes a putative autolysin. These data highlight the importance of CPS for biofilm formation and propose a potential shared ancestry of its CPS locus with .

IMPORTANCE

Diverse capsules from are vital for bacterial virulence and pathogenesis. Oral streptococci show strong responses to a wide range of pneumococcal capsule-specific sera. Yet, the evolution of this capsule diversity in relation to microbe-host interactions remains underexplored. Our research delves into the connection between commensal oral streptococcal and pneumococcal capsules, highlighting the potential for gene transfer and evolution of various capsule types. Understanding the genetic and evolutionary factors that drive capsule diversity in and its related oral species is essential for the development of effective pneumococcal vaccines. The present findings provide fresh perspectives on the cross-reactivity between commensal streptococci and , its influence on bacteria-host interactions, and the development of new strategies to manage and prevent pneumococcal illnesses by targeting and modulating commensal streptococci.