Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.

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...

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Autores principales: Nelson Frazão, N Luisa Hiller, Evan Powell, Josh Earl, Azad Ahmed, Raquel Sá-Leão, Hermínia de Lencastre, Garth D Ehrlich, Alexander Tomasz
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:b5d390fb01c2446680951d62691560dd2021-11-18T08:54:32ZVirulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.1932-620310.1371/journal.pone.0074867https://doaj.org/article/b5d390fb01c2446680951d62691560dd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24069360/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We 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 (10(5) 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 (10(3) 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.Nelson FrazãoN Luisa HillerEvan PowellJosh EarlAzad AhmedRaquel Sá-LeãoHermínia de LencastreGarth D EhrlichAlexander TomaszPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74867 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Nelson Frazão
N Luisa Hiller
Evan Powell
Josh Earl
Azad Ahmed
Raquel Sá-Leão
Hermínia de Lencastre
Garth D Ehrlich
Alexander Tomasz
Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
description 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 (10(5) 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 (10(3) 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.
format article
author Nelson Frazão
N Luisa Hiller
Evan Powell
Josh Earl
Azad Ahmed
Raquel Sá-Leão
Hermínia de Lencastre
Garth D Ehrlich
Alexander Tomasz
author_facet Nelson Frazão
N Luisa Hiller
Evan Powell
Josh Earl
Azad Ahmed
Raquel Sá-Leão
Hermínia de Lencastre
Garth D Ehrlich
Alexander Tomasz
author_sort Nelson Frazão
title Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
title_short Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
title_full Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
title_fullStr Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
title_full_unstemmed Virulence potential and genome-wide characterization of drug resistant Streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
title_sort virulence potential and genome-wide characterization of drug resistant streptococcus pneumoniae clones selected in vivo by the 7-valent pneumococcal conjugate vaccine.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/b5d390fb01c2446680951d62691560dd
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