BACKGROUND: Streptococcus pneumoniae is a significant pathogen capable of expressing protective and antigenically diverse capsules. To better understand the molecular basis of capsular antigenic diversity, we investigated the hypothetical serological role of wcjE, which encodes a capsule O-acetyltransferase, in the vaccine-targeted serotype 9V and related serotype 9A. METHODS: We inactivated wcjE by recombination in a serotype 9V strain and determined wcjE sequences of 11 serotype 9A clinical isolates. We determined the antigenic phenotypes of these pneumococcal strains with serogroup 9-specific antibodies and flow cytometry. RESULTS: Inactivation of wcjE in a serotype 9V strain resulted in expression of the 9A phenotype. Each serotype 9A clinical isolate contained a distinct mutation to wcjE. Flow cytometry showed that some 9A isolates (herein named 9Aα) expressed trace amounts of 9V-specific epitopes whereas others (named 9Aβ) did not express any. Recombination with 9Aα wcjE alleles into a 9Aβ strain conferred partial expression of 9V-specific epitopes. CONCLUSIONS: 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.
BACKGROUND:Streptococcus pneumoniae is a significant pathogen capable of expressing protective and antigenically diverse capsules. To better understand the molecular basis of capsular antigenic diversity, we investigated the hypothetical serological role of wcjE, which encodes a capsule O-acetyltransferase, in the vaccine-targeted serotype 9V and related serotype 9A. METHODS: We inactivated wcjE by recombination in a serotype 9V strain and determined wcjE sequences of 11 serotype 9A clinical isolates. We determined the antigenic phenotypes of these pneumococcal strains with serogroup 9-specific antibodies and flow cytometry. RESULTS: Inactivation of wcjE in a serotype 9V strain resulted in expression of the 9A phenotype. Each serotype 9A clinical isolate contained a distinct mutation to wcjE. Flow cytometry showed that some 9A isolates (herein named 9Aα) expressed trace amounts of 9V-specific epitopes whereas others (named 9Aβ) did not express any. Recombination with 9Aα wcjE alleles into a 9Aβ strain conferred partial expression of 9V-specific epitopes. CONCLUSIONS: 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.
Authors: Saskia van Selm; Lisette M van Cann; Marc A B Kolkman; Bernard A M van der Zeijst; Jos P M van Putten Journal: Infect Immun Date: 2003-11 Impact factor: 3.441
Authors: Allison M Brady; Juan J Calix; Jigui Yu; Kimball Aaron Geno; Gary R Cutter; Moon H Nahm Journal: J Infect Dis Date: 2014-03-27 Impact factor: 5.226
Authors: Juan J Calix; Richard J Porambo; Allison M Brady; Thomas R Larson; Janet Yother; Chitrananda Abeygunwardana; Moon H Nahm Journal: J Biol Chem Date: 2012-06-26 Impact factor: 5.157
Authors: K Aaron Geno; Gwendolyn L Gilbert; Joon Young Song; Ian C Skovsted; Keith P Klugman; Christopher Jones; Helle B Konradsen; Moon H Nahm Journal: Clin Microbiol Rev Date: 2015-07 Impact factor: 26.132
Authors: Feroze Ganaie; Karsten Maruhn; Chengxin Li; Richard J Porambo; Pernille L Elverdal; Chitrananda Abeygunwardana; Mark van der Linden; Jens Ø Duus; Carmen L Sheppard; Moon H Nahm Journal: J Clin Microbiol Date: 2021-06-18 Impact factor: 5.948