Occurrence, Distribution, and Origins of Streptococcus pneumoniae Serotype 6C, a Recently Recognized Serotype

Abstract

The prevalence of Streptococcus pneumoniae serotype 6C, a recently recognized serotype that cross-reacts serologically with serotype 6A, was investigated. Isolates of serotype 6A in various collections were recovered, and serotype 6C was differentiated from 6A by multiplex PCR of DNA extracts by using appropriate primers. Antimicrobial susceptibility was performed by Clinical and Laboratory Standards Institute broth microdilution, and selected isolates were typed by pulsed-field gel electrophoresis, repetitive sequence-based PCR typing, and rapid multilocus sequence typing (MLST) by electrospray ionization mass spectrometry of PCR products. The sources of the isolates included blood (n ‫؍‬ 5), the lower respiratory tract (n ‫؍‬ 27), the sinus (n ‫؍‬ 5), the ear (n ‫؍‬ 2), and the nasopharynx (n ‫؍‬ 18); isolates were recovered from 49 children and 11 adults. Pediatric isolates were found in all six major U.S. geographic regions. Antimicrobial susceptibility showed that 22 isolates were nonsusceptible to penicillin, macrolides, and trimethoprim-sulfamethoxazole, 8 had other resistance patterns, and 30 were fully susceptible. The three typing methods used showed similar clusters of up to eight isolates per cluster. MLST showed five clusters related to serotype 6A, two clusters related to serotype 6B, one cluster related to serotype 3, and one cluster related to serotype 34. This study documents the occurrence, nationwide distribution, diversity, likely origins, and increasing incidence after 2001 of this recently recognized serotype. Serotype 6C warrants consideration for addition to future conjugate pneumococcal vaccines.The polysaccharide capsule is the major virulence determinant of Streptococcus pneumoniae, preventing phagocytosis. A total of 25 serotypes have one antigenic capsular determinant, while 21 serogroups have a common and one or more unique determinants. The number of known capsular serotypes, which totaled 90 in 1995 (16), increased to 91 in 2007 with the description of serotype 6C (34, 35). This new serotype crossreacts serologically with serotype 6A but is differentiated by a change in the wciN gene region of the capsular locus encoding for galactosyl transferase (32).A variety of capsular serotypes have been used to develop vaccines, and two such vaccines are currently available. The first is a 23-valent purified capsular polysaccharide vaccine (Pneumovax; Merck & Co, Whitehouse Station, NJ) containing 23 serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F). The second is a 7-valent vaccine containing saccharides purified from capsular polysaccharides conjugated to a protein vector (PCV7) to provide immunity in children under 2 years of age (Prevnar; Wyeth Pharmaceuticals, Inc., Philadelphia, PA) and contains serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F.In view of the inclusion of serotype 6B in PCV7 and the inability to differentiate serotypes 6A and 6C by serotyping, we recovered and reidentified isolates previously characterized as ser...

Epidemiology of pneumococcal serotype 6A and 6C among invasive and carriage isolates from Alaska, 1986–2009

“…The presence of 8 STs found among only 27 serotype 6C isolates in this study are consistent with other studies that have described a high degree of genetic diversity among this serotype (Campos et al, 2009;Carvalho et al, 2009;Green et al, 2011;Jacobs et al, 2009;Nunes et al, 2009;Rolo et al, 2011b). Of the 8 STs of serotype 6C isolates reported in this study, 4 (1390, 1379, 473, and 1292) have been previously associated with serotype 6A.…”

“…Two major lineages accounted for 66% of these isolates (CC473 and CC460). Similar findings have been reported by Jacobs et al (2009) who found that among their serotype 6A isolates, the majority were STs 473, 460, 395, and 376. In the Carvalho et al (2009) study, 4 STs (1292, 473, 395, and376) were observed with ST376, accounting for approximately 30% of serotype 6As, including the majority of isolates fully resistant to penicillin and the majority of erythromycin-resistant isolates.…”

“…While ST2899 and ST4285 found in this study are associated solely with serotype 6C, they are double-and triple-locus variants, respectively, of ST1390. Other studies have reported similar findings Green et al, 2011;Jacobs et al, 2009). Among the serotype 6C isolates analyzed by Jacobs et al (2009), 9 MLST clusters were identified.…”

“…Other studies have reported similar findings Green et al, 2011;Jacobs et al, 2009). Among the serotype 6C isolates analyzed by Jacobs et al (2009), 9 MLST clusters were identified. Five of these clusters were related to clonal complexes associated with serotype 6A (473, 1379, 490, 690, and 1390).…”

“…Since then, there have been a number of reports detailing the prevalence, antimicrobial susceptibility patterns, and genetic diversity among serotype 6C isolates collected from both invasive disease and nasopharyngeal colonization studies (Campos et al, 2009;Carvalho et al, 2009;du Plessis et al, 2008;Green et al, 2011;Hermans et al, 2008;Jacobs et al, 2008Jacobs et al, , 2009Nahm et al, 2009;Nunes et al, 2009;Rolo et al, 2011a;Tocheva et al, 2010). In studies that looked at the prevalence of serotype 6C among invasive and carriage isolates, it was found that anywhere between 5% and 100% of isolates that originally typed as 6A were subsequently identified as serotype 6C (Campos et al, 2009;Carvalho et al, 2009;du Plessis et al, 2008;Hermans et al, 2008;Jacobs et al, 2009;Millar et al, 2010;Rolo et al, 2011a). This large range was primarily due to the fact that the proportion of serotype 6C isolates increased over time, while the proportion of serotype 6A isolates decreased.…”