Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study

Despite its inclusion in pneumococcal conjugate vaccine 13 (PCV13), Streptococcus pneumoniae serotype 3 remains a major cause of invasive pneumococcal disease in England and Wales. Previous studies have indicated that there are distinct lineages within serotype 3 clonal complex 180 and the clade distributions have shifted in recent years with the emergence of clade II. We undertook whole genome sequencing and genomic analysis of 616 serotype 3 isolates from England and Wales between 2003 and 2018, including invasive and carriage isolates. Our investigations showed that clade II has expanded since 2014 and now represents 50% of serotype 3 invasive pneumococcal disease (IPD) isolates in England and Wales. Genomic analysis of antibiotic resistance and protein antigen genes showed that distinct profiles are present within the clades which could account for the recent emergence of this clade. This investigation highlights the importance and utility of routine whole genome sequencing and its ability to identify new and emerging variation at the single nucleotide level which informs surveillance and will impact future vaccine development.

Download Full-text

Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States

Clinical Microbiology and Infection ◽

10.1016/j.cmi.2016.08.001 ◽

2016 ◽

Vol 22 (12) ◽

pp. 1002.e1-1002.e8 ◽

Cited By ~ 58

Author(s):

B.J. Metcalf ◽

S. Chochua ◽

R.E. Gertz ◽

Z. Li ◽

H. Walker ◽

...

Keyword(s):

United States ◽

Antimicrobial Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

The United States ◽

Whole Genome ◽

Resistance Determinants

Download Full-text

Streptococcus pneumoniae genomic datasets from an Indian population describing pre-vaccine evolutionary epidemiology using a whole genome sequencing approach

Microbial Genomics ◽

10.1099/mgen.0.000645 ◽

2021 ◽

Vol 7 (9) ◽

Author(s):

Geetha Nagaraj ◽

Vandana Govindan ◽

Feroze Ganaie ◽

V. T. Venkatesha ◽

Paulina A. Hawkins ◽

...

Keyword(s):

Antibiotic Resistance ◽

Streptococcus Pneumoniae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Pneumococcal Disease ◽

Age Groups ◽

Multidrug Resistant ◽

Whole Genome ◽

Genomic Study ◽

The Impact

Globally, India has a high burden of pneumococcal disease, and pneumococcal conjugate vaccine (PCV) has been rolled out in different phases across the country since May 2017 in the national infant immunization programme (NIP). To provide a baseline for assessing the impact of the vaccine on circulating pneumococci in India, genetic characterization of pneumococcal isolates detected prior to introduction of PCV would be helpful. Here we present a population genomic study of 480 Streptococcus pneumoniae isolates collected across India and from all age groups before vaccine introduction (2009–2017), including 294 isolates from pneumococcal disease and 186 collected through nasopharyngeal surveys. Population genetic structure, serotype and antimicrobial susceptibility profile were characterized and predicted from whole-genome sequencing data. Our findings revealed high levels of genetic diversity represented by 110 Global Pneumococcal Sequence Clusters (GPSCs) and 54 serotypes. Serotype 19F and GPSC1 (CC320) was the most common serotype and pneumococcal lineage, respectively. Coverage of PCV13 (Pfizer) and 10-valent Pneumosil (Serum Institute of India) serotypes in age groups of ≤2 and 3–5 years were 63–75 % and 60–69 %, respectively. Coverage of PPV23 (Merck) serotypes in age groups of ≥50 years was 62 % (98/158). Among the top five lineages causing disease, GPSC10 (CC230), which ranked second, is the only lineage that expressed both PCV13 (serotypes 3, 6A, 14, 19A and 19F) and non-PCV13 (7B, 13, 10A, 11A, 13, 15B/C, 22F, 24F) serotypes. It exhibited multidrug resistance and was the largest contributor (17 %, 18/103) of NVTs in the disease-causing population. Overall, 42 % (202/480) of isolates were penicillin-resistant (minimum inhibitory concentration ≥0.12 µg ml−1) and 45 % (217/480) were multidrug-resistant. Nine GPSCs (GPSC1, 6, 9, 10, 13, 16, 43, 91, 376) were penicillin-resistant and among them six were multidrug-resistant. Pneumococci expressing PCV13 serotypes had a higher prevalence of antibiotic resistance. Sequencing of pneumococcal genomes has significantly improved our understanding of the biology of these bacteria. This study, describing the pneumococcal disease and carriage epidemiology pre-PCV introduction, demonstrates that 60–75 % of pneumococcal serotypes in children ≤5 years are covered by PCV13 and Pneumosil. Vaccination against pneumococci is very likely to reduce antibiotic resistance. A multidrug-resistant pneumococcal lineage, GPSC10 (CC230), is a high-risk clone that could mediate serotype replacement.

Download Full-text

Expanding U.S. Laboratory Capacity for Neisseria gonorrhoeae Antimicrobial Susceptibility Testing and Whole-Genome Sequencing through the CDC's Antibiotic Resistance Laboratory Network

Journal of Clinical Microbiology ◽

10.1128/jcm.01461-19 ◽

2020 ◽

Vol 58 (4) ◽

Cited By ~ 2

Author(s):

Ellen N. Kersh ◽

Cau D. Pham ◽

John R. Papp ◽

Robert Myers ◽

Richard Steece ◽

...

Keyword(s):

Public Health ◽

Antibiotic Resistance ◽

Neisseria Gonorrhoeae ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Antimicrobial Susceptibility ◽

Susceptibility Testing ◽

Whole Genome ◽

Content Type ◽

Laboratory Capacity

ABSTRACT U.S. gonorrhea rates are rising, and antibiotic-resistant Neisseria gonorrhoeae (AR-Ng) is an urgent public health threat. Since implementation of nucleic acid amplification tests for N. gonorrhoeae identification, the capacity for culturing N. gonorrhoeae in the United States has declined, along with the ability to perform culture-based antimicrobial susceptibility testing (AST). Yet AST is critical for detecting and monitoring AR-Ng. In 2016, the CDC established the Antibiotic Resistance Laboratory Network (AR Lab Network) to shore up the national capacity for detecting several resistance threats including N. gonorrhoeae. AR-Ng testing, a subactivity of the CDC’s AR Lab Network, is performed in a tiered network of approximately 35 local laboratories, four regional laboratories (state public health laboratories in Maryland, Tennessee, Texas, and Washington), and the CDC’s national reference laboratory. Local laboratories receive specimens from approximately 60 clinics associated with the Gonococcal Isolate Surveillance Project (GISP), enhanced GISP (eGISP), and the program Strengthening the U.S. Response to Resistant Gonorrhea (SURRG). They isolate and ship up to 20,000 isolates to regional laboratories for culture-based agar dilution AST with seven antibiotics and for whole-genome sequencing of up to 5,000 isolates. The CDC further examines concerning isolates and monitors genetic AR markers. During 2017 and 2018, the network tested 8,214 and 8,628 N. gonorrhoeae isolates, respectively, and the CDC received 531 and 646 concerning isolates and 605 and 3,159 sequences, respectively. In summary, the AR Lab Network supported the laboratory capacity for N. gonorrhoeae AST and associated genetic marker detection, expanding preexisting notification and analysis systems for resistance detection. Continued, robust AST and genomic capacity can help inform national public health monitoring and intervention.

Download Full-text

Whole genome sequencing of diverse Shiga toxin-producing and non-producing Escherichia coli strains reveals a variety of virulence and novel antibiotic resistance plasmids

Plasmid ◽

10.1016/j.plasmid.2015.12.001 ◽

2016 ◽

Vol 83 ◽

pp. 8-11 ◽

Cited By ~ 12

Author(s):

Liliana Losada ◽

Chitrita DebRoy ◽

Diana Radune ◽

Maria Kim ◽

Ravi Sanka ◽

...

Keyword(s):

Escherichia Coli ◽

Antibiotic Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Shiga Toxin ◽

Whole Genome ◽

Resistance Plasmids

Download Full-text

Challenges and opportunities for whole-genome sequencing-based surveillance of antibiotic resistance

Annals of the New York Academy of Sciences ◽

10.1111/nyas.13310 ◽

2017 ◽

Vol 1388 (1) ◽

pp. 108-120 ◽

Cited By ~ 43

Author(s):

Anita C. Schürch ◽

Willem van Schaik

Keyword(s):

Antibiotic Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome ◽

Challenges And Opportunities

Download Full-text

Integrating Culture-based Antibiotic Resistance Profiles with Whole-genome Sequencing Data for 11,087 Clinical Isolates

Genomics Proteomics & Bioinformatics ◽

10.1016/j.gpb.2018.11.002 ◽

2019 ◽

Vol 17 (2) ◽

pp. 169-182 ◽

Cited By ~ 2

Author(s):

Valentina Galata ◽

Cédric C. Laczny ◽

Christina Backes ◽

Georg Hemmrich-Stanisak ◽

Susanne Schmolke ◽

...

Keyword(s):

Antibiotic Resistance ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Clinical Isolates ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data

Download Full-text

The use of whole-genome sequencing for molecular epidemiology and antimicrobial surveillance: identifying the role of IncX3 plasmids and the spread of blaNDM-4-like genes in the Enterobacteriaceae

Journal of Clinical Pathology ◽

10.1136/jclinpath-2015-203044 ◽

2015 ◽

Vol 68 (10) ◽

pp. 835-838 ◽

Cited By ~ 32

Author(s):

Björn A Espedido ◽

Borce Dimitrijovski ◽

Sebastiaan J van Hal ◽

Slade O Jensen

Keyword(s):

Antibiotic Resistance ◽

Whole Genome Sequencing ◽

Resistance Gene ◽

Genome Sequencing ◽

De Novo ◽

Antibiotic Resistance Genes ◽

Whole Genome ◽

Antimicrobial Surveillance ◽

Metropolitan Hospital ◽

Genetic Context

AimsTo characterise the resistome of a multi-drug resistant Klebsiella pneumoniae (Kp0003) isolated from an Australian traveller who was repatriated to a Sydney Metropolitan Hospital from Myanmar with possible prosthetic aortic valve infective endocarditis.MethodsKp0003 was recovered from a blood culture of the patient and whole genome sequencing was performed. Read mapping and de novo assembly of reads facilitated in silico multi-locus sequence and plasmid replicon typing as well as the characterisation of antibiotic resistance genes and their genetic context. Conjugation experiments were also performed to assess the plasmid (and resistance gene) transferability and the effect on the antibiotic resistance phenotype.ResultsImportantly, and of particular concern, the carbapenem-hydrolysing β-lactamase gene blaNDM-4 was identified on a conjugative IncX3 plasmid (pJEG027). In this respect, the blaNDM-4 genetic context is similar (at least to some extent) to what has previously been identified for blaNDM-1 and blaNDM-4-like variants.ConclusionsThis study highlights the potential role that IncX3 plasmids have played in the emergence and dissemination of blaNDM-4-like variants worldwide and emphasises the importance of resistance gene surveillance.

Download Full-text