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Intrinsic epidemicity of Streptococcus pneumoniae depends on strain serotype and antibiotic susceptibility pattern.

ABSTRACT: Streptococcus pneumoniae is a major cause of invasive diseases worldwide. It spreads through an interindividual transmission, followed by usually harmless colonization of the host. Possible transmission differences reflecting intrinsic strain features (e.g., serotype and antibiotic susceptibility) have been little studied so far. In this study, we used epidemiological data from an interventional trial of S. pneumoniae carriage among kindergartners and developed a mathematical model to estimate the transmission parameters of the different strains isolated during that study. We found small but significant transmissibility differences between the observed serotypes: serotypes 3, 6A, and 19A were found to be the most epidemic, while serotypes 23F, 9V, and 14 were the least epidemic. Further analysis indicated that, within a serotype, susceptible and resistant strains had different abilities to be transmitted. Susceptible-to-resistant transmission rate ratios were computed for five serotypes; susceptible strains were significantly more epidemic than resistant strains for serotypes 6A (mean, 1.02) and 19F (1.05). Serotype 19A resistant strains were not outcompeted by susceptible strains (0.97). Nonsignificant trends were observed for serotypes 6B (1.01) and 15A (0.98). Our results support the existence of heterogeneous abilities of the different serotypes for host-to-host transmission. They also suggest that antibiotic susceptibility within a serotype affects this transmissibility. We conclude that pneumococcal strains should not be considered equally at-risk in terms of transmission. Further quantification of strain-specific epidemic potential is needed, especially in a context of extensive use of conjugate vaccines with the aim of preventing pneumococcal infections.

SUBMITTER: Domenech de Celles M

PROVIDER: S-EPMC3195016 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Intrinsic epidemicity of Streptococcus pneumoniae depends on strain serotype and antibiotic susceptibility pattern.

Domenech de Cellès Matthieu M Opatowski Lulla L Salomon Jérôme J Varon Emmanuelle E Carbon Claude C Boëlle Pierre-Yves PY Guillemot Didier D

Antimicrobial agents and chemotherapy 20110725 11

Streptococcus pneumoniae is a major cause of invasive diseases worldwide. It spreads through an interindividual transmission, followed by usually harmless colonization of the host. Possible transmission differences reflecting intrinsic strain features (e.g., serotype and antibiotic susceptibility) have been little studied so far. In this study, we used epidemiological data from an interventional trial of S. pneumoniae carriage among kindergartners and developed a mathematical model to estimate t ...[more]

PMID: 21788454

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Project description:INTRODUCTION:Pakistan has one of the highest burdens of pneumococcal diseases in the world, but unfortunately studies in this demanding research area are limited in the region. Pneumococcal surface protein A (PspA) is the next generation pneumococcal vaccine candidate as the protein locates on the Streptococcus pneumoniae surface. Its gene, pspA, might be encoded by all pneumococci, and the protein has proven immunogenicity. The molecular characterization of PspA, pneumococcal serotype distribution and antibiotic susceptibility are important for regional diversity studies. METHODS:In this study, we examined 38 pneumococcal isolates from pneumococcal diseased (pneumonia/meningitis) patients blood or cerebrospinal fluid. There were no specific inclusion or exclusion criteria, but all the individuals [ages 1 month to 12 years (male/female)] had undergone no antibiotic treatment in at least the past 3 months and had no vaccination history. We investigated the serotype distribution, antibiotic susceptibility, prevalence of the PspA family and its active domain's fusion, expression and antigenicity. RESULTS:Our finding shows that serotype 19F is the most prevalent (23.6%) followed by 18B (15.78%) (non-vaccine type) in all isolated pneumococcal strains. All strains were susceptible to chloramphenicol and linezolid, while 80% were resistant to gentamycin. Genotyping revealed that ~ 80% (N = 31/38) of pneumococcal strains produce PspA belonging to family 2 and clade 3. We further selected three active domains of PspA (family 2 and clade 3) by in silico analysis, merged together into a fusion gene for expression study, and its antigenicity was analyzed by Western blotting. CONCLUSION:Serotypes 19F and 18B (non-vaccine type) are the most prevalent in the Pakistani pneumococcal isolates. The PspA family 2 proteins produced by Pakistani pneumococcal isolates have high sequence homologies with each other and differ from those produced by strains isolated in the rest of the world. The PspA fusion peptide had a proven antigenic response in western blotting, with no considerable correlation among pneumococcal serotypes, antibiotic susceptibility and PspA family/clade distribution.

Project description:Streptococcus pneumoniae (pneumococcus) is a major human respiratory pathogen and a leading cause of bacterial pneumonia worldwide. Small regulatory RNAs (sRNAs), which often act by posttranscriptionally regulating gene expression, have been shown to be crucial for the virulence of S. pneumoniae and other bacterial pathogens. Over 170 putative sRNAs have been identified in the S. pneumoniae TIGR4 strain (serotype 4) through transcriptomic studies, and a subset of these sRNAs has been further implicated in regulating pneumococcal pathogenesis. However, there is little overlap in the sRNAs identified among these studies, which indicates that the approaches used for sRNA identification were not sufficiently sensitive and robust and that there are likely many more undiscovered sRNAs encoded in the S. pneumoniae genome. Here, we sought to comprehensively identify sRNAs in Avery's virulent S. pneumoniae strain D39 using two independent RNA sequencing (RNA-seq)-based approaches. We developed an unbiased method for identifying novel sRNAs from bacterial RNA-seq data and have further tested the specificity of our analysis program toward identifying sRNAs encoded by both strains D39 and TIGR4. Interestingly, the genes for 15% of the putative sRNAs identified in strain TIGR4, including ones previously implicated in virulence, are not present in the strain D39 genome, suggesting that the differences in sRNA repertoires between these two serotypes may contribute to their strain-specific virulence properties. Finally, this study has identified 66 new sRNA candidates in strain D39, 30 of which have been further validated, raising the total number of sRNAs that have been identified in strain D39 to 112.IMPORTANCE Recent work has shown that sRNAs play crucial roles in S. pneumoniae pathogenesis, as inactivation of nearly one-third of the putative sRNA genes identified in one study led to reduced fitness or virulence in a murine model. Yet our understanding of sRNA-mediated gene regulation in S. pneumoniae has been hindered by limited knowledge about these regulatory RNAs, including which sRNAs are synthesized by different S. pneumoniae strains. We sought to address this problem by developing a sensitive sRNA detection technique to identify sRNAs in S. pneumoniae D39. A comparison of our data set reported here to those of other RNA-seq studies for S. pneumoniae strain D39 and TIGR4 has provided new insights into the S. pneumoniae sRNA transcriptome.

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Intrinsic epidemicity of Streptococcus pneumoniae depends on strain serotype and antibiotic susceptibility pattern.

Publications

Intrinsic epidemicity of Streptococcus pneumoniae depends on strain serotype and antibiotic susceptibility pattern.

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