Imperial College London

Dr. Elita Jauneikaite

Faculty of MedicineSchool of Public Health

Advanced Research Fellow
 
 
 
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e.jauneikaite

 
 
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Location

 

Building E - Sir Michael UrenWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

77 results found

Wan Y, Myall AC, Boonyasiri A, Bolt F, Ledda A, Mookerjee S, Weiße AY, Getino M, Turton JF, Abbas H, Prakapaite R, Sabnis A, Abdolrasouli A, Malpartida-Cardenas K, Miglietta L, Donaldson H, Gilchrist M, Hopkins KL, Ellington MJ, Otter JA, Larrouy-Maumus G, Edwards AM, Rodriguez-Manzano J, Didelot X, Barahona M, Holmes AH, Jauneikaite E, Davies Fet al., 2024, Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes., J Infect Dis

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.

Journal article

Muloi DM, Jauneikaite E, Anjum MF, Essack SY, Singleton DA, Kasudi MR, Wade MJ, Egyir B, Nunn JG, Midega JT, Peacock SJ, Feasey NA, Baker KS, Zadoks RN, SEDRIC Genomics Surveillance Working Groupet al., 2023, Exploiting genomics for antimicrobial resistance surveillance at One Health interfaces., Lancet Microbe, Vol: 4, Pages: e1056-e1062

The intersection of human, animal, and ecosystem health at One Health interfaces is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focused on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group's discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges. Embedding AMR surveillance at One Health interfaces will require the development of clear beneficial use cases, especially in low-income and middle-income countries. Evidence of directionality, risks to human and animal health, and potential trade implications were also identified by the working group as key issues. Addressing these challenges will be vital to enable genomic surveillance technology to reach its full potential for assessing the risk of transmission of AMR between the environment, animals, and humans at One Health interfaces.

Journal article

Baker KS, Jauneikaite E, Nunn JG, Midega JT, Atun R, Holt KE, Walia K, Howden BP, Tate H, Okeke IN, Carattoli A, Hsu LY, Hopkins KL, Muloi DM, Wheeler NE, Aanensen DM, Mason LCE, Rodgus J, Hendriksen RS, Essack SY, Egyir B, Halpin AL, MacCannell DR, Campos J, Srikantiah P, Feasey NA, Peacock SJ, SEDRIC Genomics Surveillance Working Groupet al., 2023, Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group., Lancet Microbe, Vol: 4, Pages: e1035-e1039

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium convened an expert working group to assess the benefits and challenges of using genomics for AMR surveillance. In this Series, we detail these discussions and provide recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR.

Journal article

Baker KS, Jauneikaite E, Hopkins KL, Lo SW, Sánchez-Busó L, Getino M, Howden BP, Holt KE, Musila LA, Hendriksen RS, Amoako DG, Aanensen DM, Okeke IN, Egyir B, Nunn JG, Midega JT, Feasey NA, Peacock SJ, SEDRIC Genomics Surveillance Working Groupet al., 2023, Genomics for public health and international surveillance of antimicrobial resistance., Lancet Microbe, Vol: 4, Pages: e1047-e1055

Historically, epidemiological investigation and surveillance for bacterial antimicrobial resistance (AMR) has relied on low-resolution isolate-based phenotypic analyses undertaken at local and national reference laboratories. Genomic sequencing has the potential to provide a far more high-resolution picture of AMR evolution and transmission, and is already beginning to revolutionise how public health surveillance networks monitor and tackle bacterial AMR. However, the routine integration of genomics in surveillance pipelines still has considerable barriers to overcome. In 2022, a workshop series and online consultation brought together international experts in AMR and pathogen genomics to assess the status of genomic applications for AMR surveillance in a range of settings. Here we focus on discussions around the use of genomics for public health and international AMR surveillance, noting the potential advantages of, and barriers to, implementation, and proposing recommendations from the working group to help to drive the adoption of genomics in public health AMR surveillance. These recommendations include the need to build capacity for genome sequencing and analysis, harmonising and standardising surveillance systems, developing equitable data sharing and governance frameworks, and strengthening interactions and relationships among stakeholders at multiple levels.

Journal article

Jauneikaite E, Baker KS, Nunn JG, Midega JT, Hsu LY, Singh SR, Halpin AL, Hopkins KL, Price JR, Srikantiah P, Egyir B, Okeke IN, Holt KE, Peacock SJ, Feasey NA, SEDRIC Genomics Surveillance Working Groupet al., 2023, Genomics for antimicrobial resistance surveillance to support infection prevention and control in health-care facilities., Lancet Microbe, Vol: 4, Pages: e1040-e1046

Integration of genomic technologies into routine antimicrobial resistance (AMR) surveillance in health-care facilities has the potential to generate rapid, actionable information for patient management and inform infection prevention and control measures in near real time. However, substantial challenges limit the implementation of genomics for AMR surveillance in clinical settings. Through a workshop series and online consultation, international experts from across the AMR and pathogen genomics fields convened to review the evidence base underpinning the use of genomics for AMR surveillance in a range of settings. Here, we summarise the identified challenges and potential benefits of genomic AMR surveillance in health-care settings, and outline the recommendations of the working group to realise this potential. These recommendations include the definition of viable and cost-effective use cases for genomic AMR surveillance, strengthening training competencies (particularly in bioinformatics), and building capacity at local, national, and regional levels using hub and spoke models.

Journal article

Wheeler NE, Price V, Cunningham-Oakes E, Tsang KK, Nunn JG, Midega JT, Anjum MF, Wade MJ, Feasey NA, Peacock SJ, Jauneikaite E, Baker KS, SEDRIC Genomics Surveillance Working Groupet al., 2023, Innovations in genomic antimicrobial resistance surveillance., Lancet Microbe, Vol: 4, Pages: e1063-e1070

Whole-genome sequencing of antimicrobial-resistant pathogens is increasingly being used for antimicrobial resistance (AMR) surveillance, particularly in high-income countries. Innovations in genome sequencing and analysis technologies promise to revolutionise AMR surveillance and epidemiology; however, routine adoption of these technologies is challenging, particularly in low-income and middle-income countries. As part of a wider series of workshops and online consultations, a group of experts in AMR pathogen genomics and computational tool development conducted a situational analysis, identifying the following under-used innovations in genomic AMR surveillance: clinical metagenomics, environmental metagenomics, gene or plasmid tracking, and machine learning. The group recommended developing cost-effective use cases for each approach and mapping data outputs to clinical outcomes of interest to justify additional investment in capacity, training, and staff required to implement these technologies. Harmonisation and standardisation of methods, and the creation of equitable data sharing and governance frameworks, will facilitate successful implementation of these innovations.

Journal article

Bhatia S, Parag KV, Wardle J, Nash RK, Imai N, Elsland SLV, Lassmann B, Brownstein JS, Desai A, Herringer M, Sewalk K, Loeb SC, Ramatowski J, Cuomo-Dannenburg G, Jauneikaite E, Unwin HJT, Riley S, Ferguson N, Donnelly CA, Cori A, Nouvellet Pet al., 2023, Retrospective evaluation of real-time estimates of global COVID-19 transmission trends and mortality forecasts, PLOS ONE, Vol: 18, ISSN: 1932-6203

Journal article

Snoek L, Karampatsas K, Bijlsma MW, Henneke P, Jauneikaite E, Khan UB, Zadoks RN, Le Doare Ket al., 2023, Meeting report: Towards better risk stratification, prevention and therapy of invasive GBS disease, ESPID research meeting May 2022., Vaccine, Vol: 41, Pages: 6137-6142

The European Society of Pediatric Infectious Diseases (ESPID) hosted the third Group B Streptococcus (GBS) Research Session in Athens on 11th May 2022, providing researchers and clinicians from around the world an opportunity to share and discuss recent advances in GBS pathophysiology, molecular and genetic epidemiology and how these new insights can help in improving prevention and control of early- and late-onset GBS disease. The meeting provided a state-of-the-art overview of the existing GBS prevention strategies and their limitations, and an opportunity to share the latest research findings. The first presentation provided an overview of current GBS prevention and treatment strategies. In the second presentation, the genomic and antimicrobial resistance profiles of invasive and colonizing GBS strains were presented. The third presentation explained the association of intrapartum antibiotic prophylaxis (IAP) with the development of late-onset disease (LOD) and the interplay of host innate immunity and GBS. The fourth presentation evaluated the role of genomics in understanding horizontal GBS transmission. The fifth presentation focused on the zoonotic links for certain GBS lineages and the last presentation described the protective role of breastmilk. Talks were followed with interactive discussions and concluded with recommendations on what is needed to further GBS clinical research; these included: (i) the development of better risk stratification methods by combining GBS virulence factors, serological biomarkers and clinical risk factors; (ii) further studies on the interplay of perinatal antimicrobials, disturbances in the development of host immunity and late-onset GBS disease; (iii) routine submission of GBS isolates to reference laboratories to help in detecting potential clusters by using genomic sequencing; (iv) collaboration in animal and human GBS studies to detect and prevent the emergence of new pathogenic sequence types; and (v) harnessing the plet

Journal article

Wan Y, Sabnis A, Mumin Z, Potterill I, Jauneikaite E, Brown CS, Ellington MJ, Edwards A, Sriskandan Set al., 2023, IS1-related large-scale deletion of chromosomal regions harbouring the oxygen-insensitive nitroreductase gene nfsB causes nitrofurantoin heteroresistance in Escherichia coli, Microbial Genomics, Vol: 9, Pages: 1-11, ISSN: 2057-5858

Nitrofurantoin is a broad-spectrum first-line antimicrobial used for managing uncomplicated urinary tract infection (UTI). Loss-of-function mutations in chromosomal genes nfsA, nfsB and ribE of Escherichia coli are known to reduce nitrofurantoin susceptibility. Here, we report the discovery of nitrofurantoin heteroresistance in E. coli clinical isolates and a novel genetic mechanism associated with this phenomenon. Subpopulations with lower nitrofurantoin susceptibility than major populations (hereafter, nitrofurantoin-resistant subpopulations) in two E. coli blood isolates (previously whole-genome sequenced) were identified using population analysis profiling. Each isolate was known to have a loss-of-function mutation in nfsA. From each isolate, four nitrofurantoin-resistant isolates were derived at a nitrofurantoin concentration of 32 mg l-1, and a comparator isolate was obtained without any nitrofurantoin exposure. Genomes of derived isolates were sequenced on Illumina and Nanopore MinION systems. Genetic variation between isolates was determined based on genome assemblies and read mapping. Nitrofurantoin minimum inhibitory concentrations (MICs) of both blood isolates were 64 mg l-1, with MICs of major nitrofurantoin-susceptible populations varying from 4 to 8 mg l-1. Two to 99 c.f.u. per million demonstrated growth at the nitrofurantoin concentration of 32 mg l-1, which is distinct from that of a homogeneously susceptible or resistant isolate. Derived nitrofurantoin-resistant isolates had 11-66 kb deletions in chromosomal regions harbouring nfsB, and all deletions were immediately adjacent to IS1-family insertion sequences. Our findings demonstrate that the IS1-associated large-scale genetic deletion is a hitherto unrecognized mechanism of nitrofurantoin heteroresistance and could compromise UTI management. Further, frequencies of resistant subpopulations from nitrofurantoin-heteroresistant isolates may cha

Journal article

Wan Y, Ganner M, Mumin Z, Ready D, Moore G, Potterill I, Paranthaman K, Jauneikaite E, Patel B, Harley A, Getino M, UKHSA S capitis Incident Management Team, Brown CS, Demirjian A, Pichon Bet al., 2023, Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom, Journal of Infection, Vol: 87, Pages: 210-219, ISSN: 0163-4453

OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005-2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection.

Journal article

Boonyasiri A, Brinkac LM, Jauneikaite E, White RC, Greco C, Seenama C, Tangkoskul T, Nguyen K, Fouts DE, Thamlikitkul Vet al., 2023, Characteristics and genomic epidemiology of colistin-resistant Enterobacterales from farmers, swine, and hospitalized patients in Thailand, 2014-2017, BMC Infectious Diseases, Vol: 23, Pages: 1-14, ISSN: 1471-2334

BACKGROUND: Colistin is one of the last resort therapeutic options for treating carbapenemase-producing Enterobacterales, which are resistant to a broad range of beta-lactam antibiotics. However, the increased use of colistin in clinical and livestock farming settings in Thailand and China, has led to the inevitable emergence of colistin resistance. To better understand the rise of colistin-resistant strains in each of these settings, we characterized colistin-resistant Enterobacterales isolated from farmers, swine, and hospitalized patients in Thailand. METHODS: Enterobacterales were isolated from 149 stool samples or rectal swabs collected from farmers, pigs, and hospitalized patients in Thailand between November 2014-December 2017. Confirmed colistin-resistant isolates were sequenced. Genomic analyses included species identification, multilocus sequence typing, and detection of antimicrobial resistance determinants and plasmids. RESULTS: The overall colistin-resistant Enterobacterales colonization rate was 26.2% (n = 39/149). The plasmid-mediated colistin-resistance gene (mcr) was detected in all 25 Escherichia coli isolates and 9 of 14 (64.3%) Klebsiella spp. isolates. Five novel mcr allelic variants were also identified: mcr-2.3, mcr-3.21, mcr-3.22, mcr-3.23, and mcr-3.24, that were only detected in E. coli and Klebsiella spp. isolates from farmed pigs. CONCLUSION: Our data confirmed the presence of colistin-resistance genes in combination with extended spectrum beta-lactamase genes in bacterial isolates from farmers, swine, and patients in Thailand. Differences between the colistin-resistance mechanisms of Escherichia coli and Klebsiella pneumoniae in hospitalized patients were observed, as expected. Additionally, we identified mobile colistin-resistance mcr-1.1 genes from swine and patient isolates belonging to plasmids of the same incompatibility group. This supported the possibility that horizontal transmission of bacterial strains or plasmid-

Journal article

Yip AYG, King OG, Omelchenko O, Kurkimat S, Horrocks V, Mostyn P, Danckert N, Ghani R, Satta G, Jauneikaite E, Davies FJ, Clarke TB, Mullish BH, Marchesi JR, McDonald JAKet al., 2023, Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites, Nature Communications, Vol: 14, Pages: 1-20, ISSN: 2041-1723

The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.

Journal article

Getino M, Stout R, Davies F, Jauneikaite Eet al., 2023, P14 Optimization of real-time sequencing for rapid detection of bacterial species and antimicrobial resistance in blood and urine infections, BSAC UTI Conference 2023, Publisher: Oxford University Press, ISSN: 2632-1823

Conference paper

Chindelevitch L, van Dongen M, Graz H, Pedrotta A, Suresh A, Uplekar S, Jauneikaite E, Wheeler Net al., 2023, Ten simple rules for the sharing of bacterial genotype-phenotype data on antimicrobial resistance, PLoS Computational Biology, Vol: 19, ISSN: 1553-734X

The increasing availability of high-throughput sequencing (frequently termed next-generation sequencing (NGS)) data has created opportunities to gain deeper insights into the mechanisms of a number of diseases and is already impacting many areas of medicine and public health. The area of infectious diseases stands somewhat apart from other human diseases insofar as the relevant genomic data comes from the microbes rather than their human hosts. A particular concern about the threat of antimicrobial resistance (AMR) has driven the collection and reporting of large-scale datasets containing information from microbial genomes together with antimicrobial susceptibility test (AST) results. Unfortunately, the lack of clear standards or guiding principles for the reporting of such data is hampering the field’s advancement. We therefore present our recommendations for the publication and sharing of genotype and phenotype data on AMR, in the form of 10 simple rules. The adoption of these recommendations will enhance AMR data interoperability and help enable its large-scale analyses using computational biology tools, including mathematical modelling and machine learning. We hope that these rules can shed light on often overlooked but nonetheless very necessary aspects of AMR data sharing and enhance the field’s ability to address the problems of understanding AMR mechanisms, tracking their emergence and spread in populations, and predicting microbial susceptibility to antimicrobials for diagnostic purposes.

Journal article

Myall A, Wiedermann M, Vasikasin P, Klamser P, Wan Y, Zachariae A, Peach R, Dorigatti I, Kreitmann L, Rodgus J, Getino-Redondo M, Mookerje S, Jauneikaite E, Davies F, Weisse A, Price J, Holmes A, Barahona M, Brockmann Det al., 2023, RECONSTRUCTING AND PREDICTING THE SPATIAL EVOLUTION OF CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE OUTBREAKS, Publisher: ELSEVIER SCI LTD, Pages: S65-S65, ISSN: 1201-9712

Conference paper

Zhi X, Li HK, Li H, Loboda Z, Charles S, Vieira A, Huse K, Jauneikaite E, Reeves L, Mok KY, Coelho J, Lamagni T, Sriskandan Set al., 2023, Emerging invasive group A Streptococcus M1UK lineage detected by allele-specific PCR, England, 2020, Emerging Infectious Diseases, Vol: 29, Pages: 1007-1010, ISSN: 1080-6040

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.

Journal article

Li H-K, Zhi X, Vieira A, Whitwell HJ, Schricker A, Jauneikaite E, Li H, Yosef A, Andrew I, Game L, Turner CE, Lamagni T, Coelho J, Sriskandan Set al., 2023, Characterisation of emergent toxigenic M1UK Streptococcus pyogenes and associated sublineages, Microbial Genomics, Vol: 9, Pages: 1-15, ISSN: 2057-5858

Streptococcus pyogenes genotype emm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm1 sublineage, M1UK, that produces increased levels of SpeA toxin was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UK is now dominant in England. To more fully characterize M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UK and contemporary non-M1UKemm1 strains (M1global). Just seven genes were differentially expressed by M1UK compared with contemporary M1global strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK (gldA, mipB/talC, pflD, and phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of gldA in M1global abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediate emm1 sublineages in England comprising 13/27 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogenetic emm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically defined medium. In rich broth, however, expression of SpeA was upregulated ~10-fold in both M123SNPs and M1UK sublineages, compared with M113SNPs and M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UK and undoubtedly important, M1UK strains have outcompeted M123SNPs and other emm types that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SN

Journal article

Khan UB, Portal EAR, Sands K, Lo S, Chalker VJ, Jauneikaite E, Spiller OBet al., 2023, Genomic analysis reveals new integrative conjugal elements and transposons in gbs conferring antimicrobial resistance, Antibiotics, Vol: 12, Pages: 1-16, ISSN: 2079-6382

Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of neonatal sepsis and increasingly found as an invasive pathogen in older patient populations. Beta-lactam antibiotics remain the most effective therapeutic with resistance rarely reported, while the majority of GBS isolates carry the tetracycline resistance gene tet(M) in fixed genomic positions amongst five predominant clonal clades. In the UK, GBS resistance to clindamycin and erythromycin has increased from 3% in 1991 to 11.9% (clindamycin) and 20.2% (erythromycin), as reported in this study. Here, a systematic investigation of antimicrobial resistance genomic content sought to fully characterise the associated mobile genetic elements within phenotypically resistant GBS isolates from 193 invasive and non-invasive infections of UK adult patients collected during 2014 and 2015. Resistance to erythromycin and clindamycin was mediated by erm(A) (16/193, 8.2%), erm(B) (16/193, 8.2%), mef(A)/msr(D) (10/193, 5.1%), lsa(C) (3/193, 1.5%), lnu(C) (1/193, 0.5%), and erm(T) (1/193, 0.5%) genes. The integrative conjugative elements (ICEs) carrying these genes were occasionally found in combination with high gentamicin resistance mediating genes aac(6′)-aph(2″), aminoglycoside resistance genes (ant(6-Ia), aph(3′-III), and/or aad(E)), alternative tetracycline resistance genes (tet(O) and tet(S)), and/or chloramphenicol resistance gene cat(Q), mediating resistance to multiple classes of antibiotics. This study provides evidence of the retention of previously reported ICESag37 (n = 4), ICESag236 (n = 2), and ICESpy009 (n = 3), as well as the definition of sixteen novel ICEs and three novel transposons within the GBS lineage, with no evidence of horizontal transfer.

Journal article

Price V, Ngwira LG, Lewis JM, Baker KS, Peacock SJ, Jauneikaite E, Feasey Net al., 2023, A systematic review of economic evaluations of whole genome sequencing for the surveillance of bacterial pathogens, Microbial Genomics, Vol: 9, ISSN: 2057-5858

Whole-genome sequencing (WGS) has unparalleled ability to distinguish between bacteria, with many public health applications. The generation and analysis of WGS data require significant financial investment. We describe a systematic review summarizing economic analyses of genomic surveillance of bacterial pathogens, reviewing the evidence for economic viability. The protocol was registered on PROSPERO (CRD42021289030). Six databases were searched on 8 November 2021 using terms related to ‘WGS’, ‘population surveillance’ and ‘economic analysis’. Quality was assessed with the Drummond–Jefferson checklist. Following data extraction, a narrative synthesis approach was taken. Six hundred and eighty-one articles were identified, of which 49 proceeded to full-text screening, with 9 selected for inclusion. All had been published since 2019. Heterogeneity was high. Five studies assessed WGS for hospital surveillance and four analysed foodborne pathogens. Four were cost–benefit analyses, one was a cost–utility analysis, one was a cost-effectiveness analysis, one was a combined cost-effectiveness and cost–utility analysis, one combined cost-effectiveness and cost–benefit analyses and one was a partial analysis. All studies supported the use of WGS as a surveillance tool on economic grounds. The available evidence supports the use of WGS for pathogen surveillance but is limited by marked heterogeneity. Further work should include analysis relevant to low- and middle-income countries and should use real-world effectiveness data.

Journal article

Harvey EJ, Ashiru-Oredope D, Hill LF, Demirjian Aet al., 2023, Need for standardized vancomycin dosing for coagulase-negative staphylococci in hospitalized infants, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 29, Pages: 10-12, ISSN: 1198-743X

Journal article

Vieira A, Soo VWC, Li HK, Zhi X, Reeves L, Huse K, Mok KY, Cowen O, Jauneikaite E, Coelho J, Sriskandan Set al., 2023, Tricontinental detection of Streptococcus pyogenes M1<sub>UK</sub>: A call for wider research and active surveillance

<h4>Summary</h4> The Streptococcus pyogenes M1 UK lineage, characterised by an intrinsic ability to express SpeA toxin and defined by 27 single nucleotide polymorphisms in the core genome, dominates the population of emm 1 S. pyogenes isolates in England. The lineage has been identified elsewhere in Europe, North America, and, most recently, Australia. SpeA however may not be the sole deterministic factor underlying success of the M1 UK lineage. Production of SpeA by strains belonging to an intermediate emm 1 sublineage, M1 23SNP , is indistinguishable from M1 UK strains. Despite this, in England at least, M1 UK has outcompeted strains from the M1 23SNP sublineage. We infer that the fitness of M1 UK resides in additional properties that confer an advantage to S. pyogenes , underlining a need for further research. A single nucleotide polymorphism (SNP) in the ssrA leader sequence upstream of speA is one of a limited number of SNPs that distinguish intermediate sublineages that differ in SpeA production. Introduction of the ssrA SNP into representative isolates of the widely disseminated M1 global clone and the intermediate M1 13SNP lineage (that cannot otherwise produce readily-detectable SpeA in culture) resulted in SpeA expression, confirming the importance of the ssrA SNP to SpeA phenotype. However, RNAseq analysis of clinical strains showed that presence of the SNP was not invariably linked to read-through from the ssrA leader sequence or SpeA expression. Literature review suggests that read through and speA mRNA transcript length may be impacted by the two component regulator CovRS, pointing to a complex regulatory network interaction between the bacterial chromosome and phage-encoded superantigens.

Working paper

Li HK, Zhi X, Vieira A, Whitwell HJ, Schricker A, Jauneikaite E, Li H, Yosef A, Andrew I, Game L, Turner CE, Lamagni T, Coelho J, Sriskandan Set al., 2022, Characterisation of emergent toxigenic M1<sub>UK</sub><i>Streptococcus pyogenes</i>and associated sublineages

<jats:title>Abstract</jats:title><jats:p><jats:italic>Emm</jats:italic>1<jats:italic>Streptococcus pyogenes</jats:italic>is a successful, globally-distributed epidemic clone that is regarded as inherently invasive. An<jats:italic>emm</jats:italic>1 sublineage, M1<jats:sub>UK</jats:sub>, that expresses increased SpeA toxin, was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1<jats:sub>UK</jats:sub>is now dominant in England. To more fully characterise M1<jats:sub>UK</jats:sub>, we undertook comparative transcriptomic and proteomic analyses of M1<jats:sub>UK</jats:sub>and contemporary non-M1<jats:sub>UK</jats:sub><jats:italic>emm</jats:italic>1 strains (M1<jats:sub>global</jats:sub>).</jats:p><jats:p>Just seven genes were differentially expressed by M1<jats:sub>UK</jats:sub>compared with contemporary M1<jats:sub>global</jats:sub>strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1<jats:sub>UK</jats:sub>(gldA, mipB/talC, pflD, and pts system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1<jats:sub>UK</jats:sub>strains have a stop codon in gldA. Deletion of the gldA gene in M1<jats:sub>global</jats:sub>abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect.</jats:p><jats:p>Phylogenetic analysis identified two intermediate<jats:italic>emm</jats:italic>1 sublineages in England comprising 13/27 (M1<jats:sub>13SNPs</jats:sub>) and 23/27 SNPs (M1<jats:sub>23SNPs</jats:sub>) respectively, that had failed to expand in the population. Proteomic analysis

Working paper

Zhi X, Li HK, Li H, Loboda Z, Charles S, Vieira A, Huse K, Jauneikaite E, Coelho J, Lamagni T, Sriskandan Set al., 2022, Ongoing emergence of M1<sub>UK</sub>lineage among invasive group A streptococcus isolates in 2020 and use of allele-specific PCR

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>An increasing burden of invasive group A streptococcal infections is reported in multiple countries, notably England, where scarlet fever cases are also abundant. In England, increased scarlet fever and invasive infections have been associated with emergence of a sublineage of<jats:italic>emm</jats:italic>1<jats:italic>Streptococcus pyogenes</jats:italic>that expresses increased SpeA scarlet fever erythrogenic toxin. Wider surveillance for toxigenic<jats:italic>Streptococcus pyogenes</jats:italic>lineage M1<jats:sub>UK</jats:sub>is much needed however, to date, lineage assignment has required genome sequencing limiting surveillance to those centres with access to such facilities.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>To circumvent the requirement for genome sequencing, an allele-specific PCR was developed to distinguish M1<jats:sub>UK</jats:sub>from other<jats:italic>emm</jats:italic>1 strains. Additional PCR assays were developed to distinguish M1<jats:sub>UK</jats:sub>from two intermediate lineages that were detected previously. The assay was evaluated using DNA from genome-sequenced upper respiratory tract<jats:italic>emm</jats:italic>1<jats:italic>S. pyogenes</jats:italic>strains and a further set of 16 genome-sequenced invasive<jats:italic>S. pyogenes</jats:italic>isolates that included the two intermediate lineages. The assay was then applied to DNA from all 305 invasive<jats:italic>emm</jats:italic>1 isolates that had been submitted to the reference laboratory in the one pear period Jan 1-Dec 31 2020, in order to assign lineage.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The allele sp

Journal article

Rodgus J, Prakapaite R, Mitsidis P, Grigaleviciute R, Planciuniene R, Kavaliauskas P, Jauneikaite Eet al., 2022, Molecular epidemiology of Group B streptococci in Lithuania identifies multi-drug resistant clones and sporadic ST1 serotypes Ia and Ib, Pathogens, Vol: 11, Pages: 1-11, ISSN: 2076-0817

Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of neonatal infections. Yet, detailed assessment of the genotypic and phenotypic factors associated with GBS carriage, mother-to-baby transmission, and GBS infection in neonates and adults is lacking. Understanding the distribution of GBS genotypes, including the predominance of different serotypes, antimicrobial resistance (AMR) genes, and virulence factors, is likely to help to prevent GBS diseases, as well as inform estimates of the efficacy of future GBS vaccines. To this end, we set out to characterise GBS isolates collected from pregnant and non-pregnant women in Kaunas region in Lithuania. Whole genome sequences of 42 GBS isolates were analysed to determine multi-locus sequence typing (MLST), the presence of acquired AMR and surface protein genes, and the phylogenetic relatedness of isolates. We identified serotypes Ia (42.9%, 18/42), III (33.3%, 14/42), V (21.4%, 9/42), and a single isolate of serotype Ib. Genomic analyses revealed high diversity among isolates, with 18 sequence types (STs) identified, including three novel STs. 85.7% (36/42) of isolates carried at least one AMR gene: tetM or tetO (35/42), ermB or lsaC (8/42) and ant6-Ia and aph3-III (2/42). This study represents the first genomic analysis of GBS isolated from women in Lithuania and contributes to an improved understanding of the global spread of GBS genotypes and phenotypes, laying the foundations for future GBS surveillance in Lithuania.

Journal article

Jauneikaite E, Honeyford K, Blandy O, Mosavie M, Pearson M, Ramzan FA, Ellington M, PARKHILL J, Costelloe C, Woodford N, Sriskandan Set al., 2022, Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular-epidemiological study, Journal of Antimicrobial Chemotherapy, Vol: 77, Pages: 1753-1761, ISSN: 0305-7453

Objectives:Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of multi-drug resistant lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. Methods:We genome sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned multi-locus sequence types, virulence factors, and AMR genes to all isolates. Isolate sequence types were then linked to phenotypic antimicrobial susceptibility, patient demographic, and clinical outcome data to explore relationships between the E. coli sequence types, patient factors, and outcomes. Results:A total of 551 E. coli genomes were analysed. Four sequence types (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin-clavulanic acid, gentamicin, and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length-of-stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli sequence type and mortality. Several unexpected associations were identified between gentamicin non-susceptibility; ethnicity; sex and adverse outcomes, requiring further research.Conclusions:Although E. coli sequence type was associated with defined antimicrobial non-susceptibility patterns and prolonged length-of-stay, E. coli sequence type was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of beta-lactam agents with gentamicin.

Journal article

Imai N, Gaythorpe K, Bhatia S, Mangal T, Cuomo-Dannenburg G, Unwin H, Jauneikaite E, Ferguson NMet al., 2022, COVID-19 in Japan, January – March 2020: insights from the first three months of the epidemic, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334

Background:Understanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. Methods:We conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. Results:The corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period (16 – 23 March 2020), Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age with individuals more likely to infect, and be infected by, contacts in a similar age group to them. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.Conclusions:Information collected in the early phases of an out

Journal article

Taylor E, Jauneikaite E, Sriskandan S, Woodford N, Hopkins KLet al., 2022, Novel 16S rRNA methyltransferase RmtE3 in acinetobacter baumannii ST79., Journal of Medical Microbiology, Vol: 71, ISSN: 0022-2615

Introduction. The 16S rRNA methyltransferase (16S RMTase) gene armA is the most common mechanism conferring high-level aminoglycoside resistance in Acinetobacter baumannii, although rmtA, rmtB, rmtC, rmtD and rmtE have also been reported.Hypothesis/Gap statement. The occurrence of 16S RMTase genes in A. baumannii in the UK and Republic of Ireland is currently unknown.Aim. To identify the occurrence of 16S RMTase genes in A. baumannii isolates from the UK and the Republic of Ireland between 2004 and 2015.Methodology. Five hundred and fifty pan-aminoglycoside-resistant A. baumannii isolates isolated from the UK and the Republic of Ireland between 2004 and 2015 were screened by PCR to detect known 16S RMTase genes, and then whole-genome sequencing was conducted to screen for novel 16S RMTase genes.Results. A total of 96.5 % (531/550) of isolates were positive for 16S RMTase genes, with all but 1 harbouring armA (99.8 %, 530/531). The remaining isolates harboured rmtE3, a new rmtE variant. Most (89.2 %, 473/530) armA-positive isolates belonged to international clone II (ST2), and the rmtE3-positive isolate belonged to ST79. rmtE3 shared a similar genetic environment to rmtE2 but lacked an ISCR20 element found upstream of rmtE2.Conclusion. This is the first report of rmtE in A. baumannii in Europe; the potential for transmission of rmtE3 to other bacterial species requires further research.

Journal article

Cordery R, Purba A, Begum L, Mills E, Mosavie M, Vieira A, Jauneikaite E, Leung RCY, Siggins M, Ready D, Hoffman P, Lamagni T, Sriskandan Set al., 2022, Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK, The Lancet Microbe, Vol: 3, Pages: e366-e375, ISSN: 2666-5247

BackgroundDespite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014 and 2018. We aimed to assess the effects of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments to inform future guidance.MethodsWe did a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in six settings across five schools in Greater London, UK. Schools and nurseries were eligible to participate if they had reported two cases of scarlet fever within 10 days of each other among children aged 2–8 years from the same class, with the most recent case arising in the preceding 48 h. We cultured throat swabs from children with scarlet fever, classroom contacts, and household contacts at four timepoints. We also cultured hand swabs and cough plates from all cases in years 1 and 2 of the study, and from classroom contacts in year 2. Surface swabs from toys and other fomites in classrooms were cultured in year 1, and settle plates from classrooms were collected in year 2. Any sample with S pyogenes detected was recorded as positive and underwent emm genotyping and genome sequencing to compare with the outbreak strain.FindingsSix classes, comprising 12 cases of scarlet fever, 17 household contacts, and 278 classroom contacts were recruited between March 1 and May 31, 2018 (year 1), and between March 1 and May 31, 2019 (year 2). Asymptomatic throat carriage of the outbreak strains increased from 11 (10%) of 115 swabbed children in week 1, to 34 (27%) of 126 in week 2, to 26 (24%) of 108 in week 3, and then five (14%) of 35 in week 4. Compared with carriage of outbreak S pyogenes strains, colonisation with non-outbreak and non-genotyped S pyogenes strains occurred in two (2%) of 115 swabbed children in week 1, five (4%) of 126 in week 2, six (6%) of 108 in week 3, and in none of the 35 children in week 4

Journal article

Ledda A, Cummins M, Shaw LP, Jauneikaite E, Cole K, Lasalle F, Barry D, Turton J, Rosmarin C, Anaraki S, Wareham D, Stoesser N, Paul J, Manuel R, Cherian BP, Didelot Xet al., 2022, Hospital outbreak of carbapenem-resistant Enterobacterales associated with a bla OXA-48 plasmid carried mostly by Escherichia coli ST399, Microbial Genomics, Vol: 8, ISSN: 2057-5858

A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.

Journal article

Khan U, Jauneikaite E, Andrews R, Chalker V, Owen Set al., 2022, Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the United Kingdom between 2014 and 2015, Microbial Genomics, Vol: 8, ISSN: 2057-5858

Cases of invasive Group B Streptococcal infections in the adult UK population have steadily increased over recent years, with most common serotypes being V, III and Ia, but less is known of the genetic background of these strains. We have carried out in-depth analysis of whole genome sequences of 193 clinically important GBS isolates (186 were from invasive and 7 were from non-invasive infection) isolated from adults and submitted to the National Reference Laboratory at UK Health Security Agency between January 2014 and December 2015. We have determined that capsular serotypes III (26.8%), Ia (26.2%) and V (14.9%) were most commonly identified, with slight differences in gender and age distribution. Most isolates (n=185) grouped to 5 clonal complexes: CC1, CC8, CC17, CC19 and CC23 with common associations between specific serotypes and virulence genes. Additionally, we have identified large recombination events mediating potential capsular switching events between ST1 serotype V and serotypes Ib (n=2 isolates), II (n=2 isolates) and VI (n=2 isolates); ST19 serotype III and serotype V (n=5 isolates); CC17 serotype III and serotype IV (n=1 isolate).The high genetic diversity of disease-causing isolates and multiple recombination events reported in this study, highlight the need for routine surveillance of the circulating disease-causing GBS strains. This information is crucial to better understand global spread of GBS serotypes and genotypes and will form the baseline information for any future GBS vaccine research in the UK and worldwide. Impact statementThis study is the first study to report on in-depth genomic analysis of the disease-causing GBS in adult population in the UK. We describe the most common serotype-genotype combinations, including multi-locus sequence types (MLST) and major virulence gene combinations for the specific serotypes, found in our dataset. Importantly, we report on various potential capsular type switching caused by recombination events fo

Journal article

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