Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Genome Medicine

Research

Marco R. Oggioni¹  Joshua C. D’Aeth²  Alexandru V. Ion²  Min Jung Kwun²  Nicholas J. Croucher²  Sam Dougan³  David A. Goulding³  Stephen D. Bentley³  Hsueh-Chien Cheng³ 

[1] Department of Genetics, University of Leicester, University Road, LE1 7RH, Leicester, UK;Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Irnerio 42, 40126, Bologna, Italy;MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, White City Campus, Imperial College London, W12 0BZ, London, UK;Parasites & Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, Cambridge, UK;

关键词: Genomic epidemiology;    Pneumococcus;    Vaccine;    Prophage;    Transformation;    Recombination;    Non-coding RNA;    Selfish DNA;   

DOI  :  10.1186/s13073-022-01147-2

 received in 2022-08-09, accepted in 2022-11-29,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).MethodsA genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain’s evolution.ResultsGPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade’s composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.ConclusionThis interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.

【 授权许可】

CC BY   
© The Author(s) 2022

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