Skip to main content

Abstract

WHO has identified high priority pathogens to guide research, and drug discovery and development[i]. Through the widespread use of genome sequencing, researchers are tracking the spread of bacteria around the globe to inform public health interventions[ii]. International studies are expanding the promise of routine whole-genome sequencing (WGS) of bacterial pathogens for epidemiological surveillance, outbreak detection, and infection control[iii].

As part of an ecosystem approach, CGPS has close working partnerships with WHO and public health authorities, including the US Centre for Disease Control, the European CDC, and Public Health England. With these international partners, CGPS contributed to important epidemiological findings for high priority pathogens.

Main Article

For example, a European survey of the priority pathogen Klebsiella pneumoniae found that within-hospital and interhospital spread to be more frequent than the spread between countries[iv], an important insight for local interventions and control. A study of Staphylococcus aureus found that pathogen surveillance plays a critical role in the early identification of emerging clones that have jumped host[v].

Analyzing 1200 cholera samples from 14 South American and 45 African countries covering a 49-year period, a major genomic study showed that humans, not reservoirs, drive cholera epidemics with both the South American and African epidemics triggered by human transmission of the disease, not environmental reservoirs or climate events. This discovery will help focus control strategies on areas of greatest impact[vi].

These international partnerships are significant contributors to the global reservoir of information.

Working with the European Centre for Disease Control and collaborators, the genomes of 1,054 samples of N_. gonorrhoeae_ from 20 countries have been sequenced with the bacteria’s phenotypic and epidemiological data. The result is an easily accessible, online map of antibiotic resistance of the bacteria across the continent which has been made open-access in PathogenWatch, enabling researchers to rapidly share, compare and interrogate their data[vii].

A European survey of the priority pathogen Klebsiella pneumoniae made available through Microreact includes the phylogenetic analysis of the isolates together with all metadata and links to raw sequence data[iv].

The results of these partnerships?

The greatest impact has been on the development of global genomic data. Microreact includes data visualizations for COVID-19 pandemic, the West African Ebola epidemic, and the Zika virus in the Americas; and Pathogenwatch now provides species and taxonomy prediction for over 60,000 variants of bacteria, viruses, and fungi.

Importantly, global genomic data enables extended analysis. The routine use of whole-genome sequencing, for example, provides an opportunity to leverage artificial intelligence and machine learning to better understand how bacteria become dangerous[viii] . A machine learning program has been trained using the genome sequences of Salmonella enterica strains, which causes mild food poisoning, but which can also cause serious infections such as typhoid.

With research partners, a study identified almost 200 genes involved in controlling whether the bacterium will cause food poisoning or an invasive infection, and patterns of genetic changes which were associated with a bacteria evolving to become more dangerous[ii]. Importantly, the machine learning tool is not limited in its use and has been used to study emerging antibiotic resistance in other countries.

References

[i] WHO 2017. Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. WHO Geneva.
[ii] Wheeler N et al. 2018. Machine learning identifies signatures of host adaptation in the bacterial pathogen Salmonella in Wellcome Sanger Institute Highlights 2018/19
[iii] Aanensen et al. ESCMID Study Group on Molecular Epidemiological Markers (ESGEM), European Staphylococcal Reference Laboratory Working Group. 2016. Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive Staphylococcusaureus in Europe.mBio7(3)
[iv] David et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nature Microbiology Vol 4 November 2019.
[v] Richardson et al. 2018. Gene exchange drives the ecological success of a multi-host bacterial pathogen. Nature, Ecology and Evolution | VOL 2 | September 2018
[vi] Domman D et al. Integrated view of Vibrio cholerae in the Americas. Science. 2017; 358: 789–793.
[vii] Harris SR et al. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. Lancet Infectious Diseases 2018; 18 in in Wellcome Sanger Institute Highlights 2018/19
[viii] Wheeler, N. 2019. Tracing outbreaks with machine learning. Nature reviews | Microbiology