Rebecca Ashley Gladstone

• Pöntinen, Anna Kaarina; Gladstone, Rebecca Ashley; Pesonen, Henri; Pesonen, Maiju; Cleon, Francois Pierre Alexandre & Parcell, Benjamin J [Show all 14 contributors for this article] (2024). Modulation of multidrug-resistant clone success in Escherichia coli populations: a longitudinal, multi-country, genomic and antibiotic usage cohort study. Lancet Microbe. ISSN 2666-5247. 5(2), p. e142–e150. doi: 10.1016/S2666-5247(23)00292-6.
• Alonso, Sergio Arredondo; Gladstone, Rebecca Ashley; Pöntinen, Anna Kaarina; Gama, João Alves; Schürch, Anita C. & Lanza, Val F. [Show all 10 contributors for this article] (2023). Mge-cluster: a reference-free approach for typing bacterial plasmids. NAR Genomics and Bioinformatics. ISSN 2631-9268. 5(3). doi: 10.1093/nargab/lqad066. Full text in Research Archive
• Alonso, Sergio Arredondo; Blundell-Hunter, George; Fu, Zuyi; Gladstone, Rebecca Ashley; Fillol-Salom, Alfred & Loraine, Jessica [Show all 25 contributors for this article] (2023). Evolutionary and functional history of the Escherichia coli K1 capsule. Nature Communications. ISSN 2041-1723. 14(1). doi: 10.1038/s41467-023-39052-w. Full text in Research Archive
• Tonkin-Hill, Gerry; Gladstone, Rebecca Ashley; Pöntinen, Anna Kaarina; Alonso, Sergio Arredondo; Bentley, Stephen D. & Corander, Jukka (2023). Robust analysis of prokaryotic pangenome gene gain and loss rates with Panstripe. Genome Research. ISSN 1088-9051. 33(1), p. 129–140. doi: 10.1101/gr.277340.122. Full text in Research Archive
• Mai, The Tien; Lees, John A; Gladstone, Rebecca Ashley & Corander, Jukka (2023). Inferring the heritability of bacterial traits in the era of machine learning. Bioinformatics Advances. ISSN 2635-0041. 3(1). doi: 10.1093/bioadv/vbad027. Full text in Research Archive
• Mäklin, Tommi; Thorpe, Harry Arthur Frank Wright; Pöntinen, Anna Kaarina; Gladstone, Rebecca Ashley; Shao, Yan & Pesonen, Maiju [Show all 12 contributors for this article] (2022). Strong pathogen competition in neonatal gut colonisation. Nature Communications. ISSN 2041-1723. 13(1). doi: 10.1038/s41467-022-35178-5. Full text in Research Archive Show summary

  Opportunistic bacterial pathogen species and their strains that colonise the human gut are generally understood to compete against both each other and the commensal species colonising this ecosystem. Currently we are lacking a population-wide quantification of strain-level colonisation dynamics and the relationship of colonisation potential to prevalence in disease, and how ecological factors might be modulating these. Here, using a combination of latest high-resolution metagenomics and strain-level genomic epidemiology methods we performed a characterisation of the competition and colonisation dynamics for a longitudinal cohort of neonatal gut microbiomes. We found strong inter- and intra-species competition dynamics in the gut colonisation process, but also a number of synergistic relationships among several species belonging to genus Klebsiella, which includes the prominent human pathogen Klebsiella pneumoniae. No evidence of preferential colonisation by hospital-adapted pathogen lineages in either vaginal or caesarean section birth groups was detected. Our analysis further enabled unbiased assessment of strain-level colonisation potential of extra-intestinal pathogenic Escherichia coli (ExPEC) in comparison with their propensity to cause bloodstream infections. Our study highlights the importance of systematic surveillance of bacterial gut pathogens, not only from disease but also from carriage state, to better inform therapies and preventive medicine in the future.

• Lo, Stephanie W; Mellor, Kate; Cohen, Robert; Alonso, Alba Redin; Belman, Sophie & Kumar, Narender [Show all 39 contributors for this article] (2022). Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study. Lancet Microbe. ISSN 2666-5247. 3(10), p. e735–e743. doi: 10.1016/S2666-5247(22)00158-6. Full text in Research Archive Show summary

  Background Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. Methods Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). Findings Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3–5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. Interpretation Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. Funding Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention.

• Egorova, Ekaterina; Kumar, Narender; Gladstone, Rebecca Ashley; Urban, Yulia; Voropaeva, Elena & Chaplin, A.V. [Show all 14 contributors for this article] (2022). Key features of pneumococcal isolates recovered in Central and Northwestern Russia in 2011–2018 determined through whole-genome sequencing. Microbial Genomics. ISSN 2057-5858. 8(9). doi: 10.1099/mgen.0.000851. Full text in Research Archive Show summary

  Invasive pneumococcal disease remains one of the leading causes of morbidity and mortality worldwide. In Russia, 13- valent pneumococcal conjugate vaccine (PCV13) was introduced into the childhood immunization programme nationwide in 2014. As part of the Global Pneumococcal Sequencing Project (GPS), we used genome data to characterize 179 pneumococcal isolates collected from Russia in 2011–2018 to investigate the circulating pneumococcal strains using a standardized genomic definition of pneumococcal lineages (global pneumococcal sequence clusters, GPSCs), prevalent serotypes and antimicrobial resistance profiles. We observed high serotype and lineage diversity among the 179 isolates recovered from cerebrospinal fluid (n=77), nasopharyngeal swabs (n=99) and other non-sterile site swabs (n=3). Overall, 60 GPSCs were identified, including 48 clonal complexes (CCs) and 14 singletons, and expressed 42 serotypes (including non-typable). Among PCV13 serotypes, 19F, 6B and 23F were the top three serotypes while 11A, 15B/C and 8 were the top three among non-PCV13 serotypes in the collection. Two lineages (GPSC6 and GPSC47) expressed both PCV13 and non-PCV13 serotypes that caused invasive disease, and were penicillin- and multidrug-resistant (MDR), highlighting their potential to adapt and continue to cause infections under vaccine and antibiotic selective pressure. PCV13 serotypes comprised 92 % (11/12) of the CSF isolates from the children aged below 5 years; however, the prevalence of PCV13 serotype isolates dropped to 53 % (31/58) among the nasopharyngeal isolates. Our analysis showed that 59 % (105/179) of the isolates were predicted to be non-susceptible to at least one class of antibiotics and 26 % (46/179) were MDR. Four MDR lineages (GPSC1, GPSC6, GPSC10 and GPSC47) accounted for 65 % (30/46) of the MDR isolates and expressed PCV13 serotypes (93 %, 28/30). This study provides evidence of high genetic and serotype diversity contributed by a mix of globally spreading and regionally circulating lineages in Russia. The observations suggest that the PCV13 vaccine could be important in reducing both invasive disease and antimicrobial resistance. We also identify potential lineages (GPSC6 and GPSC47) that may evade the vaccine.

• Cleary, David W.; Jones, Jessica; Gladstone, Rebecca Ashley; Osman, Karen L.; Devine, Vanessa T. & Jefferies, Johanna M. [Show all 9 contributors for this article] (2022). Changes in serotype prevalence of Streptococcus pneumoniae in Southampton, UK between 2006 and 2018. Scientific Reports. ISSN 2045-2322. 12(1). doi: 10.1038/s41598-022-17600-6. Full text in Research Archive Show summary

  treptococcus pneumoniae continues to cause significant disease burden. Whilst pneumococcal conjugate vaccines (PCV) have substantially reduced this burden, serotype replacement partially negates this success due to increased disease associated with non-vaccine serotypes (NVTs). Continued surveillance is therefore essential to provide crucial epidemiological data. Annual cross-sectional surveillance of paediatric pneumococcal carriage was started in Southampton, UK following PCV7 roll-out in 2006. Nasopharyngeal swabs were collected from children < 5 years old each winter (October to March) from 2006/07 and for each consecutive year until 2017/18. Pneumococcal serotype was inferred from whole genome sequencing data. A total of 1429 (32.5%) pneumococci were isolated from 4093 children. Carriage ranged from 27.8% (95%CI 23.7–32.7) in 2008/09 to 37.9% (95%CI 32.8–43.2) in 2014/15. Analyses showed that carriage increased in children aged 24–35 months (p < 0.001) and 47–60 months (p < 0.05). Carriage of PCV serotypes decreased markedly following PCV7 and/or PCV13 introduction, apart from serotype 3 where the relative frequency was slightly lower post-PCV13 (pre-PCV13 n = 7, 1.67%; post-PCV13 n = 13, 1.27%). Prevalence of NVTs implicated in increased disease was low with 24F (n = 19, 1.4%) being the most common followed by 9N (n = 11, 0.8%), 8 (n = 7, 0.5%) and 12F (n = 3, 0.2%).

• Belman, Sophie; Soeng, Sona; Soputhy, Chansovannara; Gladstone, Rebecca Ashley; Hawkins, Paulina A. & Breiman, Robert F. [Show all 10 contributors for this article] (2022). Genetic background of Cambodian pneumococcal carriage isolates following pneumococcal conjugate vaccine 13. Microbial Genomics. ISSN 2057-5858. 8(6). doi: 10.1099/mgen.0.000837. Full text in Research Archive Show summary

  Streptococcus pneumoniae (the pneumococcus) is a leading cause of childhood mortality globally and in Cambodia. It is commensal in the human nasopharynx, occasionally resulting in invasive disease. Monitoring population genetic shifts, characterized by lineage and serotype expansions, as well as antimicrobial-resistance (AMR) patterns is crucial for assessing and predicting the impact of vaccination campaigns. We sought to elucidate the genetic background (global pneumococcal sequence clusters; GPSCs) of pneumococci carried by Cambodian children following perturbation by pneumococcal conjugate vaccine (PCV) 13. We sequenced pre-PCV13 (01/2013–12/2015, N=258) and post-PCV13 carriage isolates (01/2016–02/2017, N=428) and used PopPUNK and SeroBA to determine lineage prevalence and serotype composition. Following PCV13 implementation in Cambodia, we saw expansions of non-vaccine type (NVT) serotypes 23A (GPSC626), 34 (GPSC45) and 6D (GPSC16). We predicted antimicrobial susceptibility using the CDC-AMR pipeline and determined concordance with phenotypic data. The CDC-AMR pipeline had >90 % concordance with the phenotypic antimicrobial-susceptibility testing. We detected a high prevalence of AMR in both expanding non-vaccine serotypes and residual vaccine serotype 6B. Persistently high levels of AMR, specifically persisting multidrug-resistant lineages, warrant concern. The implementation of PCV13 in Cambodia has resulted in NVT serotype expansion reflected in the carriage population and driven by specific genetic backgrounds. Continued monitoring of these GPSCs during the ongoing collection of additional carriage isolates in this population is necessary.

• Chaguza, Chrispin; Ebruke, Chinelo; Senghore, Madikay; Lo, Stephanie W.; Tientcheu, Peggy-Estelle & Gladstone, Rebecca Ashley [Show all 21 contributors for this article] (2022). Comparative Genomics of Disease and Carriage Serotype 1 Pneumococci. Genome Biology and Evolution (GBE). ISSN 1759-6653. 14(4). doi: 10.1093/gbe/evac052. Full text in Research Archive
• Gladstone, Rebecca Ashley; Siira, Lotta; Brynildsrud, Ola Brønstad; Vestrheim, Didrik Frimann; Turner, Paul & Clarke, S.C. [Show all 21 contributors for this article] (2021). International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease. Vaccine. ISSN 0264-410X. 40(7), p. 1054–1060. doi: 10.1016/j.vaccine.2021.10.046. Full text in Research Archive Show summary

  Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. Results: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. Conclusion: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

• Corcoran, Mary; Mereckiene, Jolita; Cotter, Suzanne; Murchan, Stephen; Lo, Stephanie & McGee, Lesley [Show all 11 contributors for this article] (2021). Using genomics to examine the persistence of Streptococcus pneumoniae serotype 19A in Ireland and the emergence of a sub-clade associated with vaccine failures. Vaccine. ISSN 0264-410X. 39(35), p. 5064–5073. doi: 10.1016/j.vaccine.2021.06.017. Full text in Research Archive
• Alonso, Sergio Arredondo; Pöntinen, Anna Kaarina; Cleon, Francois Pierre Alexandre; Gladstone, Rebecca Ashley; Schürch, Anita C. & Johnsen, Pål Jarle [Show all 8 contributors for this article] (2021). A high-throughput multiplexing and selection strategy to complete bacterial genomes. GigaScience. ISSN 2047-217X. 10(12), p. 1–13. doi: 10.1093/gigascience/giab079. Full text in Research Archive
• Pöntinen, Anna Kaarina; Top, Janetta; Alonso, Sergio Arredondo; Tonkin-Hill, Gerry; Freitas, Ana R. & Novais, Carla [Show all 21 contributors for this article] (2021). Apparent nosocomial adaptation of Enterococcus faecalis predates the modern hospital era. Nature Communications. ISSN 2041-1723. 12. doi: 10.1038/s41467-021-21749-5. Full text in Research Archive
• Gladstone, Rebecca Ashley; McNally, Alan; Pöntinen, Anna Kaarina; Tonkin-Hill, Gerry; Lees, John A. & Skytén, Kusti Onni [Show all 29 contributors for this article] (2021). Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002–17: a nationwide, longitudinal, microbial population genomic study. Lancet Microbe. ISSN 2666-5247. 2(7), p. e331–e341. doi: 10.1016/S2666-5247(21)00031-8. Full text in Research Archive Show summary

  Background The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology. Methods This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017. 15 of 22 laboratories were able to share their isolates, and the first 22·5% of isolates from each year were requested. We used whole genome sequencing to infer the population structure (PopPUNK), and we investigated the clade composition of the dominant multidrug resistant clonal complex (CC)131 using genetic markers previously reported for sequence type (ST)131, effective population size (BEAST), and presence of determinants of antimicrobial resistance (ARIBA, PointFinder, and ResFinder databases) over time. We compared these features between the 2002–10 and 2011–17 time periods. We also compared our results with those of a longitudinal study from the UK done between 2001 and 2011. Findings Of the 3500 isolates requested from the participating laboratories, 3397 (97·1%) were received, of which 3254 (95·8%) were successfully sequenced and included in the analysis. A significant increase in the number of multidrug resistant CC131 isolates from 71 (5·6%) of 1277 in 2002–10 to 207 (10·5%) of 1977 in 2011–17 (p<0·0001), was the largest clonal expansion. CC131 was the most common clone in extended-spectrum β-lactamase (ESBL)-positive isolates (75 [58·6%] of 128) and fluoroquinolone non-susceptible isolates (148 [39·2%] of 378). Within CC131, clade A increased in prevalence from 2002, whereas the global multidrug resistant clade C2 was not observed until 2007. Multiple de-novo acquisitions of both blaCTX-M ESBL-encoding genes in clades A and C1 and gain of phenotypic fluoroquinolone non-susceptibility across the clade A phylogeny were observed. We estimated that exponential increases in the effective population sizes of clades A, C1, and C2 occurred in the mid-2000s, and in clade B a decade earlier. The rate of increase in the estimated effective population size of clade A (Ne=3147) was nearly ten-times that of C2 (Ne=345), with clade A over-represented in Norwegian CC131 isolates (75 [27·0%] of 278) compared with the UK study (8 [5·4%] of 147 isolates). Interpretation The early and sustained establishment of predominantly antimicrobial susceptible CC131 clade A isolates, relative to multidrug resistant clade C2 isolates, suggests that resistance is not necessary for clonal success. However, even in the low antibiotic use setting of Norway, resistance to important antimicrobial classes has rapidly been selected for in CC131 clade A isolates. This study shows the importance of genomic surveillance in uncovering the complex ecology underlying multidrug resistance dissemination and competition, which have implications for the design of strategies and interventions to control the spread of high-risk multidrug resistant clones.

• Tonkin-Hill, Gerry; MacAlasdair, Neil; Ruis, Christopher; Weimann, Aaron; Horesh, Gal & Lees, John A. [Show all 14 contributors for this article] (2020). Producing polished prokaryotic pangenomes with the Panaroo pipeline. Genome Biology. ISSN 1465-6906. 21, p. 1–21. doi: 10.1186/s13059-020-02090-4. Full text in Research Archive

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• Karlsen, Miriam Kristine; Pöntinen, Anna Kaarina; Gladstone, Rebecca Ashley; Alves Gama, Joao Pedro & Fredheim, Elizabeth Gladys Aarag (2023). Biofilm-associated traits of human pathogenic Escherichia coli.
• Kristine Karlsen, Miriam; Pöntinen, Anna Kaarina; Gama, João Alves; Gladstone, Rebecca Ashley; Sørum, Vidar & Fredheim, Elizabeth G. Aarag (2022). Disclosing the biofilmome of Escherichia coli.
• Kristine Karlsen, Miriam; Pöntinen, Anna Kaarina; Gama, João Alves; Gladstone, Rebecca Ashley; Sørum, Vidar & Fredheim, Elizabeth G. Aarag (2022). Disclosing the biofilmome of Escherichia coli.
• Kristine Karlsen, Miriam; Pöntinen, Anna Kaarina; Gama, João Alves; Gladstone, Rebecca Ashley; Sørum, Vidar & Fredheim, Elizabeth G. Aarag (2022). Disclosing the biofilmome of Escherichia coli.
• Gladstone, Rebecca Ashley; McNally, Alan; Johnsen, Pål Jarle; Samuelsen, Ørjan & Corander, Jukka (2021). Antimicrobial resistance genes and clonal success in Escherichia coli isolates causing bloodstream infection – Authors’ reply. Lancet Microbe. ISSN 2666-5247. 2(10). doi: 10.1016/S2666-5247(21)00176-2.

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