In collaboration with Pacific Biosciences (PacBio), Menlo Park, Calif, researchers at the Wellcome Sanger Institute, Hinxton, UK, have sequenced the genomes of more than 3,000 bacteria, including some of the world’s most dangerous. The bacteria collected by the National Collection of Type Cultures (NCTC) include deadly strains of cholera, dysentery, and plague that infect tens of millions of people worldwide every year.
By decoding the DNA of such bacteria, researchers expect to better understand the diseases they cause and how they develop resistance to antibiotics. The genomic maps, which are publicly available, could also lead to the development of new diagnostic tests, treatments, or vaccines.
The NCTC was established in 1920, and currently houses more than 5,500 species of bacteria, making it the most enduring and largest collection of clinically relevant bacteria in the world. Its extensive use enables researchers to compare historical and modern strains to advance global knowledge of the epidemiology, virulence, prevention, and treatment of infectious diseases.
Antibiotic resistance is a significant global problem, and the collection includes some of the most important known drug-resistant bacteria. These include tuberculosis, one of the top ten causes of death worldwide, infecting 10.4 million and killing 1.7 million people in 2016 alone; and gonorrhea, the sexually transmitted disease that infects 78 million people per year and is now becoming extremely difficult to treat.1,2 The NCTC also contains samples of methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to multiple antibiotics and can cause life-threatening infections in hospitals. Genetic study of these strains will help researchers to understand the mechanisms of antibiotic resistance, and to look for any cracks in their armor to enable treatment.
The initiative also sequenced all of the collection’s ‘type strains’ of bacteria, which are the first strains used to describe and classify each species. The genome sequences of these highly valuable strains are fundamental for developing ways to identify specific infections in people, including tests to diagnose bacterial infections in the field, rapidly identify the source of an outbreak, and help contain infections.
The many strains of historical importance in the collection include 16 strains deposited by penicillin discoverer Alexander Fleming, including a sample taken from his own nose. Also notable is the first bacterium to be deposited in the NCTC: a strain of dysentery-causing Shigella flexneri isolated in 1915 from a soldier in the trenches of World War I.3
“Historical collections such as the NCTC are of enormous value in understanding current pathogens,” says Julian Parkhill, PhD, head of pathogen genomics at the Wellcome Sanger Institute. “Knowing very accurately what bacteria looked like before and during the introduction of antibiotics and vaccines, and comparing them to current strains from the same collection, shows us how they have responded to these treatments. This in turn helps us develop new antibiotics and vaccines. PacBio’s comprehensive DNA sequencing enables deep genomic analyses, and we are happy to be partnering with them for this important project.”
“The high-quality genomic maps enabled by SMRT sequencing allow an unprecedented understanding of these bacteria,” notes Jonas Korlach, PhD, CEO of PacBio. “We are delighted to be chosen by institutions like Wellcome Sanger to help create such essential resources for the scientific and public health communities.”
“This resource is a vital tool for public health and by sequencing the bacteria, we have made the NCTC collection ready for the 21st century so that the research community can track and understand the bacteria,” says Julie Russell, head of culture collections for the national infection service of Public Health England. “With this collection, we are providing tools for tracing infections, and identifying outbreaks of resistant bacteria, transforming public health in the UK.”
Going forward, all the bacterial species in the NCTC collection will be sequenced upon collection. Researchers can order bacterial strains from the NCTC website. Full information about each strain, including their DNA sequences, is available via the European Bioinformatics Institute.
1. Tuberculosis [online]. Geneva: World Health Organization, 2018. Available at: www.who.int/en/news-room/fact-sheets/detail/tuberculosis. Accessed July 7, 2018.
2. Antibiotic-resistant gonorrhoea on the rise, new drugs needed [online]. Geneva: World Health Organization, 2017. Available at: www.who.int/en/news-room/detail/07-07-2017-antibiotic-resistant-gonorrhoea-on-the-rise-new-drugs-needed. Accessed July 7, 2018.
3. World war I soldier helps in fight against dysentery [online]. Hinxton, UK: Wellcome Sanger Institute, 2014. Available at: www.sanger.ac.uk/news/view/2014-11-07-world-war-I-soldier-helps-in-fight-against-dysentery. Accessed July 7, 2018.