Tuberculosis resistance diagnostics have greatly improved in recent years as a result of the development of standardized phenotypic and molecular testing methods. These methods, however, are either slow or limited in the number of resistant genotypes that they can detect. With the advent of next-generation sequencing (NGS), we can avoid all of these issues because we can sequence whole tuberculosis genomes at decreasing costs and with decreasing amounts of DNA.
The researchers hope that their genome-assembly tool will accelerate the development of new antibiotics for bacterial infections. Researchers have created a novel genome assembly tool that could aid in the development of new tuberculosis and other bacterial infection treatments.
According to researchers whose findings were published in Nature Communications, the new tool, which improved the genome map of one tuberculosis strain, should do the same for other strains and bacteria.
According to the World Health Organization, Mycobacterium tuberculosis, the bacteria that causes tuberculosis, infects about a quarter of the world’s population and will kill 1.6 million people by 2021. Current medical interventions are limited to a century-old vaccine that reduces infection risk by 20% and four to six months of strong antibiotics, which can be ineffective at times.
The key to beating this disease is to understand it, and the key to understanding it lies in its DNA. We hope our new pipeline provides researchers around the world with the information they need to create faster, more effective treatments and, ideally, a fully effective vaccine.
David Alland
“The key to beating this disease is to understand it, and the key to understanding it lies in its DNA,” said David Alland, the senior author of the study who is chief of the Division of Infectious Diseases at Rutgers New Jersey Medical School and director of the school’s Public Health Research Institute. “We hope our new pipeline provides researchers around the world with the information they need to create faster, more effective treatments and, ideally, a fully effective vaccine.”
Scientists first sequenced the genome of one tuberculosis strain – H37Rv – in 1998, but they never could generate the sort of complete and accurate sequence that would maximize their chances of eradicating the disease – until now.
The new pipeline, dubbed Bact-Builder, combines common open-source genome assembly programs into a novel and easy-to-use tool which is freely available on GitHub.
Scientists today typically sequence new bacterial genomes by cutting large pieces of DNA into small, quick-to-scan fragments and then using a reference sequence such as H37Rv to align all the resulting pieces of data properly. However, assembling genomes without a reference, as Bact-Builder does with data from MinION sequencers, allows researchers to identify genes present in clinical strains that may not be present in the reference.
The tuberculosis sequence created by Bact-Builder contains approximately 6,400 thousand more pieces of information (base pairs) than the old reference and, more importantly, identifies gene new genes and gene fragments missing in the old reference.
“Just publishing a fully accurate genome for the H37Rv reference strain, which is used in hundreds of studies a year, should significantly help tuberculosis research,” Alland said.
Having an easy way to sequence all strains accurately is even more important, Alland said, “because strain comparison should answer many vital questions such as why some strains are more contagious than others. Why do some strains cause more serious disease? Why are some strains more difficult to cure? The answers to all these questions, which could help us devise better treatments and vaccines, are in the genetic code, but you need an accurate way to find them.”
