Abstract
We used mouse models of pneumococcal colonization and disease combined with full genome sequencing to characterize three major drug resistant clones of S. pneumoniae that were recovered from the nasopharynx of PCV7-immunized children in Portugal. The three clones – serotype 6A (ST2191), serotype 15A (ST63) and serotype 19A (ST276) carried some of the same drug resistance determinants already identified in nasopharyngeal isolates from the pre-PCV7 era. The three clones were able to colonize efficiently the mouse nasopharyngeal mucosa where populations of these pneumococci were retained for as long as 21 days. During this period, the three clones were able to asymptomatically invade the olfactory bulbs, brain, lungs and the middle ear mucosa and established populations in these tissues. The virulence potential of the three clones was poor even at high inoculum (105 CFU per mouse) concentrations in the mouse septicemia model and was undetectable in the pneumonia model. Capsular type 3 transformants of clones 6A and 19A prepared in the laboratory produced lethal infection at low cell concentration (103 CFU per mouse) but the same transformants became impaired in their potential to colonize, indicating the importance of the capsular polysaccharide in both disease and colonization. The three clones were compared to the genomes of 56 S. pneumoniae strains for which sequence information was available in the public databank. Clone 15A (ST63) only differed from the serotype 19F clone G54 in a very few genes including serotype so that this clone may be considered the product of a capsular switch. While no strain with comparable degree of similarity to clone 19A (ST276) was found among the sequenced isolates, by MLST this clone is a single locust variant (SLV) of Denmark14-ST230 international clone. Clone 6A (ST2191) was most similar to the penicillin resistant Hungarian serotype 19A clone.
Highlights
The nasopharynx of preschool age children, those attending day-care, is the main ecological niche for the gram-positive pathogen Streptococcus pneumoniae that asymptomatically colonizes these individuals at high rates [1]
The PCV7 vaccine did not change the overall pneumococcal carriage rate (68.2% in the vaccines and 67.6% in the control) and importantly did not change the carriage rate of drug resistant strains (37.4% in the vaccines and 39.3% in the control). We focused on the latter finding and concluded that the PCV7 vaccine led to a replacement of drug resistant strains expressing PCV7 serotypes by drug resistant strains exhibiting non-PCV7 capsular types
The commercial introduction of the 7-valent antipneumococcal conjugate vaccine (PCV7) in Portugal, in 2001, caused an extensive change in the nature of S. pneumoniae strains colonizing the nasopharynx of pre-school aged children, which represents the major natural reservoir of this bacterial pathogen [1,37,38]
Summary
The nasopharynx of preschool age children, those attending day-care, is the main ecological niche for the gram-positive pathogen Streptococcus pneumoniae that asymptomatically colonizes these individuals at high rates [1]. S. pneumoniae is a genetically diverse species capable of expressing over 90 different capsular types [6], only a limited number of these serotypes associated to a few pandemic clones have been responsible for the increase of drug resistant strains worldwide [4]. The “birthplace” of these drug resistant clones is believed to be the nasopharynx of young children, with a predisposition for upper-respiratory diseases and behavior traits that favor person-to-person contacts. These circumstances, combined with frequent antibiotic use, constitute ideal conditions for the selection, amplification and transmission of drug resistant clones [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
