Streptococcus pneumoniae Serotype 9A Isolates Contain Diverse Mutations to wcjE That Result in Variable Expression of Serotype 9V-specific Epitope

Abstract

Each serotype 9A strain independently arose from a serotype 9V strain. Furthermore, clinical isolates identified as 9A can contain mutations to wcjE that are either partially functional or completely nonfunctional, demonstrating a previously unidentified antigenic heterogeneity of serotype 9A isolates.

Biochemical, Genetic, and Serological Characterization of Two Capsule Subtypes among Streptococcus pneumoniae Serotype 20 Strains

“…Factor serum 20b does not bind serotype 33F but does bind serotype 33A, whose cps locus contains an intact wcjE gene and is otherwise identical to the 33F cps locus (11). We have identified the loss of wcjE-mediated O-acetylation as a source of structural and serological heterogeneity in serogroup 11 and serogroup 9 (2,17,20,25). Although the PS structure of serotype 33A remains to be elucidated, serotypes 33A and 33F probably follow a similar wcjE-associated phenomenon.…”

“…Mutations in the cps locus can directly translate to changes in capsular PS biochemical structure and antigenicity. For example, serologically distinct capsule types can arise because of inactivation of cps genes (2,20,21), because of incorporation of foreign genes into the cps locus (22), or by cps enzyme point mutations that modify carbohydrate substrate identity or glycosidic linkages (23). Loss of function mutation in whaF correlates with the loss of an ␣Glc residue in the serogroup 20 PS repeat unit.…”

Spectrum of Pneumococcal Serotype 11A Variants Results from Incomplete Loss of Capsule O -Acetylation

“…The 9V strains evolve serotype 9A expression following mutation of wcjE and resulting loss of capsule ␤ManNAc-6-O-acetylation (6,15). Akin to 11Av isolates, 9Vv (previously 9A␣) isolates express reduced amounts of serotype 9V-specific epitopes according to FCSA, in a wcjE allele-dependent fashion (6). Based on our studies with 11A, 11E, and 11Av, we propose that pneumococcal serotypes 9V and 9A also form two extremes of an antigenic spectrum with intermediate serovariants.…”

“…Loss of capsule expression was verified by colony morphology and the Quellung reaction using factor serum 11c, which contains antibodies that bind to serotype 11A, 11C, 11D, and 11E capsule PSs (3). The serotype 9V strain JC01 is described elsewhere (6).…”

“…Hyp11AM1 produces IgM monoclonal antibody (MAb) and Hyp11AG2 produces IgG MAb. Hybridoma supernatants containing MAbs were used in a flow cytometric serotyping assay (FCSA), as described previously (3,6). Briefly, bacteria (1 ϫ 10 7 CFU/ml) were incu- (2,5,6).…”