title: Nontypeable pneumococcal isolates among navajo and white mountain apache communities: are these really a cause of invasive disease?
abstract: BACKGROUND
  Pneumococci could evade pneumococcal conjugate vaccines (PCV) by modifying, mutating, or deleting vaccine-serotype capsule genes or by downregulating capsule production. We sought to assess whether pneumococci that are nontypeable (NT) by the Quellung reaction truly lack capsule genes or are failing to produce capsule in vitro.
  
  
  METHODS
  We applied multilocus sequence typing and a microarray for detection of pneumococcal polysaccharide capsule biosynthesis genes to NT carriage (children aged <5 years; years 1997-2000, 2006-2008) and NT invasive disease (IPD) (all ages; years 1994-2007) isolates from Native American communities.
  
  
  RESULTS
  Twenty-seven of 28 (96.4%) NT IPD isolates had sequence types (STs) typically found among typeable IPD isolates and contained whole or fragments of capsule genes that matched known serotypes; 1 NT-IPD isolate had a profile resembling NT carriage isolates. Forty-nine of 76 (64.5%) NT carriage isolates had STs that typically lack capsule genes and were similar to NT carriage isolates found globally.
  
  
  CONCLUSIONS
  This is the first documentation of IPD from an NT strain confirmed to lack all known capsule genes. Most NT IPD isolates have or had the capacity to produce capsule, whereas a majority of NT carriage isolates lack this capacity. We found no evidence of pneumococcal adaptation to PCV7 via downregulation or deletion of vaccine-serotype capsule genes.
authors.affiliation: Center for American Indian Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Scott
authors.forename: Jason
authors.initials: J
authors.lastname: Hinds
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Gould
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Millar
authors.forename: Raymond
authors.initials: R
authors.lastname: Reid
authors.forename: Mathuram
authors.initials: M
authors.lastname: Santosham
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
authors.forename: William P
authors.initials: WP
authors.lastname: Hanage
mesh_terms: D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D006801:Humans; D007198:Indians, North American; D058885:Multilocus Sequence Typing / Q000379:methods; D011008:Pneumococcal Infections / Q000208:ethnology* / Q000821:virology*; D012703:Serotyping / Q000379:methods; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000302:isolation & purification
chemical_list: D036022:Capsid Proteins