Genomic analysis of nontypeable pneumococci causing invasive pneumococcal disease in South Africa, 2003–2013

Abstract

BackgroundThe capsular polysaccharide is the principal virulence factor of Streptococcus pneumoniae and a target for current pneumococcal vaccines. However, some pathogenic pneumococci are serologically nontypeable [nontypeable pneumococci (NTPn)]. Due to their relative rarity, NTPn are poorly characterized, and, as such, limited data exist which describe these organisms. We aimed to describe disease and genotypically characterize NTPn causing invasive pneumococcal disease in South Africa.ResultsIsolates were detected through national, laboratory-based surveillance for invasive pneumococcal disease in South Africa and characterized by whole genome analysis. We predicted ancestral serotypes (serotypes from which NTPn may have originated) for Group I NTPn using multilocus sequence typing and capsular region sequence analyses. Antimicrobial resistance patterns and mutations potentially causing nontypeability were identified. From 2003–2013, 39 (0.1 %, 39/32,824) NTPn were reported. Twenty-two (56 %) had partial capsular genes (Group I) and 17 (44 %) had complete capsular deletion of which 15 had replacement by other genes (Group II). Seventy-nine percent (31/39) of our NTPn isolates were derived from encapsulated S. pneumoniae. Ancestral serotypes 1 (27 %, 6/22) and 8 (14 %, 3/22) were most prevalent, and 59 % (13/22) of ancestral serotypes were serotypes included in the 13-valent pneumococcal conjugate vaccine. We identified a variety of mutations within the capsular region of Group I NTPn, some of which may be responsible for the nontypeable phenotype. Nonsusceptibility to tetracycline and erythromycin was higher in NTPn than encapsulated S. pneumoniae.ConclusionsNTPn are currently a rare cause of invasive pneumococcal disease in South Africa and represent a genetically diverse collection of isolates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2808-x) contains supplementary material, which is available to authorized users.

Genome-wide epistasis and co-selection study using mutual information

“…This suggests non-typeable S. pneumoniae are not simply bacteria that have lost their capsule, but have also undergone other adaptive changes in specialising to a distinct niche. This may account for the distinct pathogenesis of unencapsulated strains, which do not cause severe invasive disease ( 30 ), but are known to cause outbreaks of conjunctivitis ( 31 ).…”

Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia

“…This may be because their role in disease has been limited. For example, in South Africa over a 10-year period spanning from before to after PCV, and in the United States over a 3-year period in the post-PCV era, nontypeables rarely caused disease [44, 45]. We nonetheless advocate for the inclusion of nontypeable strains in epidemiological surveillance studies owing to their increasing importance and potential for maintaining transmission.…”

Mucosal Infections and Invasive Potential of Nonencapsulated Streptococcus pneumoniae Are Enhanced by Oligopeptide Binding Proteins AliC and AliD

“…PspK has been described as an adhesin that allows NESp to colonize as efficiently as encapsulated pneumococci ( 14 , 15 ). Remarkably, extensive surveillance of invasive pneumococcal disease (IPD) isolates has revealed an association of invasive disease with NESp expressing oligopeptide binding proteins AliC and AliD despite the absence of a protective, antiphagocytic capsule thought to be necessary to establish IPD ( 12 , 16 – 20 ). A survey of pneumococcal isolates in Switzerland from 1998 to 2002 first exposed the isolation of NESp expressing AliC and AliD from a blood sample ( 12 ).…”

“…Surveillance of IPD isolates in the United States from 2006 to 2009 identified that 67% of pneumococcal isolates lacking cps genes encoded both aliC and aliD in their cps locus ( 19 ). In a surveillance study spanning 2003 to 2013 in South Africa, 82% of NESp IPD isolates with complete deletion of cps genes were described as containing aliC and aliD in place of their cps genes ( 20 ). Collectively, the isolation of IPD-associated NESp expressing AliC and AliD from geographically distinct areas of isolation suggests that these oligopeptide binding proteins afford a selective advantage during invasive disease.…”