Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study

Lo, Stephanie; Mellor, Kate C.; Cohen, Robert; Alonso, Alba Redin; Belman, Sophie; Kumar, Narender; Hawkins, Paulina A.; Gladstone, Rebecca A.; Gottberg, Anne von; Veeraraghavan, Balaji; Ravikumar, K L; Kandasamy, Rama; Pollard, Sir Andrew J; Saha, Samir K.; Bigogo, Godfrey; Antonio, Martín; Kwambana-Adams, Brenda; Mirza, Shaper; Shakoor, Sadia; Nisar, Imran; Cornick, Jennifer; Lehmann, Deborah; Ford, Rebecca; Sigaùque, Betuel; Turner, Paul; Moïsi, Jennifer C; Obaro, Stephen K.; Dagan, Ron; Diawara, Idrissa; Skoczyńska, Anna; Wang, Hui; Carter, Philip E.; Klugman, Keith P.; Rodgers, Gail L.; Breiman, Robert F.; McGee, Lesley; Bentley, Stephen D.; Almagro, Carmen Muñoz; Varon, Emmanuelle; Brooks, Abdullah; Corso, Alejandra; Davydov, Alexander; Maguire, Alison J.; Kiran, Anmol; Moiane, Benild; Beall, Bernard; Zhao, Chunjiang; Aanensen, David M.; Everett, Dean; Faccone, Diego; Foster-Nyarko, Ebenezer; Bojang, Ebrima; Егорова, Е. А.; Воропаева, Е. А.; Sampane-Donkor, Eric; Sadowy, Ewa; Nagaraj, Geetha; Mucavele, Hélio; Belabbès, Houria; Elmdaghri, Naima; Verani, Jennifer R.; Keenan, Jeremy D.; Lees, John A.; Bhai, Jyothish; Ndlangisa, Kedibone; Zerouali, Khalid; Bentley, Leon J.; Titov, Leonid; Gouveia, Linda de; Alaerts, Maaike; Ip, Margaret; Brandileone, Maria Cristina de Cunto; Hasanuzzaman, Md.; Paragi, Metka; Nurse-Lucas, Michele; Plessis, Mignon du; Ali, Mushal; Croucher, Nicholas J.; Wolter, Nicole; Givon-Lavi, Noga; Porat, Nurit; Eser, Özgen Köseoğlu; Ho, Pak‐Leung; Akpaka, Patrick Eberechi; Gagetti, Paula; Tientcheu, Peggy-Estelle; Law, Pierra Y.; Benisty, Rachel; Mostowy, Rafal; Malaker, Roly; Almeida, Samanta Cristine Grassi; Doiphode, Sanjay; Madhi, Shabir А.; Sekaran, Shamala Devi; Clarke, Stuart C.; Srifuengfung, Somporn; Nzenze, Susan; Kastrin, Tamara; Ochoa, Theresa J.; Hryniewicz, Waleria; Urban, Yu.N.

doi:10.1016/s2666-5247(22)00158-6

Cited by 49 publications

(31 citation statements)

References 48 publications

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“…Presence of these antibiotic resistance genes indicates that these GPSC types can be frequently associated with resistance to tetracycline and macrolides. In fact, our study findings validate the widespread antibiotic resistance commonly associated with GPSC10 [4].…”

Section: Antibiotic Resistance Genessupporting

confidence: 81%

“…For example, the combination GPSC1-19F (CC320) was most frequent, while GPSC10 (CC230) consisted of both vaccine and non-vaccine serotypes [17]. The GPSC10 clone is also a high risk clone with high rates of drug resistance, and is also identified as a major challenging clone for vaccine introduction [4]. The pangenome contains all the genes identified among multiple strains within a bacterial species.…”

Section: Discussionmentioning

confidence: 99%

“…The GPSC10 is predominantly associated with non-vaccine serotypes, and contains the CC230 clonal complex that emerged as the multidrug resistant clone post-PCV10 introduction in USA. Recently, the GPSC10-24F is identified as the most prevalent non-vaccine type with high rates of multidrug resistance [4]. The GPSCs are also associated with various metabolic genotypes (MT-types), indicating a difference in metabolic control which can impact the strain replacement when under competition from a different MT type [5].…”

Section: Introductionmentioning

confidence: 99%

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Comparative pangenome analysis of major pneumococcal genotypes from India

Murthy Peela,

Sistla

2024

Preprint

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Background: Pneumococcal genomes are highly dynamic with varying core genome sizes. The genotype classification system, Global Pneumococcal Sequence Clusters, identified patterns within genotype and antibiotic resistance. Few genotypes like GPSC10 are frequently associated with antimicrobial resistance and high rates of non-vaccine serotypes. Objective: To identify and annotate the differences in the core genomes of major GPSC in India, and construct and analyse the Indian Pneumococcal Pangenome (IPPG). Methods: Using existing dataset from the Global Pneumococcal Sequencing Project, 618 strains were included. The most frequent GPSCs: GPSC1, GOSC2, GPSC8, GPSC9 and GPSC10 were analyzed separately. Pangenomes were constructed using Panaroo with tuning the family threshold parameter. Differences in protein clusters were identified using Orthovenn3 webserver. Functional annotations were performed by eggNOG, Uniprot and STRING database searches. Results: The IPPG core genome size (1615 genes) was similar to those reported previously, with similar distribution of metabolic categories across the five GPSC types. The GPSC10 (1619 genes) and GPSC1 (1909 genes) had the lowest and highest core genome sizes respectively, and these core genomes possessed genes encoding for macrolide and tetracycline resistance. Virulence genes ply, psaA, pce (cbpE), pavA, nanB, lytA, and hysA are detected among all the core genomes. Conclusions: There is a genotype specific variation within the core genomes of major GPSCs in India. The presence of antibiotic resistance genes among GPSC1 and GPSC10 core genomes explain widespread drug resistance due to these genotypes. The core virulence genes identified among all the genotypes indicate conserved pathogenesis mechanisms, and can be targets for vaccine development or therapy.

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Section: Antibiotic Resistance Genessupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative pangenome analysis of major pneumococcal genotypes from India

Murthy Peela,

Sistla

2024

Preprint

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“…Among serotype 24F strains, a predominant lineage, GPSC10, has been identified in France. 28 This lineage has been transmitted in Europe and other continents. Concerningly, this serotype is frequently multidrug-resistant and is not included in most of the upcoming PCVs.…”

Section: Discussionmentioning

confidence: 99%

Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network

Rybak,

Ouldali,

Varon

et al. 2023

Pediatric Infectious Disease Journal

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Background: In France, vaccination has been implemented against Hi serotype b (Hib), pneumococcus with pneumococcal conjugate vaccines (PCV), and Neisseria meningitidis serogroup C (MenC). These interventions with different coverage and uptake have disrupted the epidemiology of vaccine-preventable acute bacterial meningitis (ABM). Methods: We analyzed data from a French prospective surveillance network of ABM in children ≤15 years old enrolled by 259 pediatric wards (estimated national coverage: 61%). From 2001 to 2020, the effect of vaccine implementation was estimated with segmented linear regression. Results: We analyzed 7,186 cases, mainly due to meningococcus (35.0%), pneumococcus (29.8%), and Hi (3.7%). MenC ABM incidence decreased (−0.12%/month, 95% CI: −0.17 to −0.07, P < 0.001) with no change for the overall meningococcal ABM when comparing the pre-MenC vaccination and the post-MenC vaccination trends. Despite a decreasing MenB ABM incidence without a vaccination program (−0.43%/month, 95% CI: −0.53 to −0.34, P < 0.001), 68.3% of meningococcal ABM involved MenB. No change in pneumococcal ABM incidence was observed after the PCV7 recommendation. By contrast, this incidence significantly decreased after the switch to PCV13 (−0.9%/month, 95% CI: −1.6 to −0.2%, P = 0.01). After May 2014, a rebound occurred (0.5%/month, 95% CI: 0.3–0.8%, P < 0.001), with 89.5% of non-PCV13 vaccine serotypes. Hib ABM incidence increased after June 2017. Conclusions: PCV7 and MenC vaccine introduction in France, with slow vaccine uptake and low coverage, had no to little impact as compared to the switch from PCV7 to PCV13, which occurred when coverage was optimal. Our data suggest that MenB and next-generation PCVs could prevent a large part of the ABM incidence in France.

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“…Consequently, vaccinetargeted serotypes have been replaced through the expansion of already common serotypes not included in current formulations, and the emergence of previously rare or unknown serotypes, changing the frequency of antimicrobial resistance (AMR) and incidence of disease in S. pneumoniae (8)(9)(10). Ongoing serotype surveillance is critical to identify significant increases in non-vaccine serotype prevalence, particularly if such a serotype is associated with AMR or high invasiveness (11). Such dynamics can be monitored through analysis of nasopharyngeal samples, although the frequent carriage of multiple serotypes within a single individual, known as 'co-carriage' or 'co-colonisation', makes identification of all circulating serotypes challenging (12).…”

Section: Introductionmentioning

confidence: 99%

Graph-based Nanopore Adaptive Sampling with GNASTy enables sensitive pneumococcal serotyping in complex samples

Horsfield,

Fok,

et al. 2024

Preprint

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Serotype surveillance of Streptococcus pneumoniae (the pneumococcus) is critical for understanding the effectiveness of current vaccination strategies. However, existing methods for serotyping are limited in their ability to identify co-carriage of multiple pneumococci and detect novel serotypes. To develop a scalable and portable serotyping method that overcomes these challenges, we employed Nanopore Adaptive Sampling (NAS), an on-sequencer enrichment method which selects for target DNA in real-time, for direct detection of S. pneumoniae in complex samples. Whereas NAS targeting the whole S. pneumoniae genome was ineffective in the presence of non-pathogenic streptococci, the method was both specific and sensitive when targeting the capsular biosynthetic locus (CBL), the operon that determines S. pneumoniae serotype. NAS significantly improved coverage and yield of the CBL relative to sequencing without NAS, and accurately quantified the relative prevalence of serotypes in samples representing co-carriage. To maximise the sensitivity of NAS to detect novel serotypes, we developed and benchmarked a new pangenome-graph algorithm, named GNASTy. We show that GNASTy outperforms the current NAS implementation, which is based on linear genome alignment, when a sample contains a serotype absent from the database of targeted sequences. The methods developed in this work provide an improved approach for novel serotype discovery and routine S. pneumoniae surveillance that is fast, accurate and feasible in low resource settings. GNASTy therefore has the potential to increase the density and coverage of global pneumococcal surveillance.

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Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study

Cited by 49 publications

References 48 publications

Comparative pangenome analysis of major pneumococcal genotypes from India

Comparative pangenome analysis of major pneumococcal genotypes from India

Vaccine-preventable Pediatric Acute Bacterial Meningitis in France: A Time Series Analysis of a 19-Year Prospective National Surveillance Network

Graph-based Nanopore Adaptive Sampling with GNASTy enables sensitive pneumococcal serotyping in complex samples

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