Abstract
Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease (IPD) in West Africa, with ST618 being the dominant cause of IPD in The Gambia. Recently however, a rare example of clonal replacement was observed, where the ST3081 clone of serotype 1 replaced the predominant ST618 clone as the main cause of IPD. In the current study, we sought to find the reasons for this unusual replacement event. Using whole-genome sequence analysis and clinically relevant models of in vivo infection, we identified distinct genetic and phenotypic characteristics of the emerging ST3081 clone. We show that ST3081 is significantly more virulent than ST618 in models of invasive pneumonia, and is carried at higher densities than ST618 during nasopharyngeal carriage. We also observe sequence type-specific accessory genes and a unique sequence type-specific fixed mutation in the pneumococcal toxin pneumolysin, which is associated with increased hemolytic activity in ST3081 and may contribute to increased virulence in this clone. Our study provides evidence that, within the same serotype 1 clonal complex, biological properties differ significantly from one clone to another in terms of virulence and host invasiveness, and that these differences may be the result of key genetic differences within the genome.
Highlights
To date, nearly 100 distinct serotypes of Streptococcus pneumoniae have been reported [1,2,3,4,5,6,7]
Imported clones have little impact on the epidemiology of serotype 1, but we recently reported clonal replacement in serotype 1 in The Gambia where the ST3081 clone replaced the predominant ST618 as the main cause of invasive pneumococcal disease (IPD) [24]. The reasons for this were unknown,. We investigated whether this clonal replacement event was a consequence of the presence of virulence associated genes in the accessory genome of ST3081, which were absent in the accessory genome of ST618
When >1 isolate was obtained during an illness episode, for example from blood and cerebrospinal fluid, only a single isolate was included in the study collection, except when the isolates differed in multilocus sequence type (MLST) or antibiotic susceptibility profile
Summary
Nearly 100 distinct serotypes of Streptococcus pneumoniae (pneumococcus) have been reported [1,2,3,4,5,6,7]. Imported clones have little impact on the epidemiology of serotype 1, but we recently reported clonal replacement in serotype 1 in The Gambia where the ST3081 clone replaced the predominant ST618 as the main cause of IPD [24]. The reasons for this were unknown, . We investigated whether this clonal replacement event was a consequence of the presence of virulence associated genes in the accessory genome of ST3081, which were absent in the accessory genome of ST618 To this end, we describe the population structure of invasive S. pneumoniae serotype 1 isolates collected in The Gambia over a 20-year period between January 1995 and December 2014, and. 1318 JID 2017:216 (15 November) Bricio-Moreno et al Downloaded from https://academic.oup.com/jid/article-abstract/216/10/1318/4158233 by London School of Hygiene & Tropical Medicine user on 18 January 2018 compare the genomic profiles and in vivo virulence, colonization and invasiveness of these 2 important evolving clones
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