Antibiotic resistance is one of the biggest threats to health today. Now, scientists at University College London and Great Ormond Street Hospital have found a way to establish which bacteria are likely to become resistant to antibiotics in the future, which could help doctors select the best treatments for infections.
Tuberculosis is a bacterial lung infection that is estimated to have killed more than one billion people over the past 200 years and is still one of the world’s most deadly diseases. In fact, in 2020 it was the second leading infectious cause of death after COVID-19, killing 1.5 million people.
While tuberculosis can be cured with the right antibiotics, treatment can take a long time and many people do not have access to good healthcare. Drug-resistant tuberculosis can develop when people do not complete their course of treatment, or when effective drugs are not available.
Tuberculosis that is resistant to multiple drugs is a huge burden on healthcare and totally drug-resistant strains have been detected in a handful of countries. As the world struggles to cope with the pandemic, progress on tuberculosis treatment has slowed.
In order to develop a better understanding of, and ultimately better treatments for, tuberculosis, this new research has identified how to pre-empt drug-resistant mutations before they occur. The researchers have termed this concept ‘pre-resistance’: when a disease-causing pathogen has a greater inherent risk of developing resistance to drugs in the future.
To find out which strains of tuberculosis bacteria showed pre-resistance to antibiotics, the researchers, in collaboration with the Peruvian Tuberculosis Programme, sequenced the genomes of 3,135 tuberculosis samples taken from the suburbs of Lima, Peru, over a 17-year period.
They then compared these samples to create a tuberculosis family tree to identify key changes in the genetic codes of the bacteria that went on to develop drug resistance. They described how variations in the tuberculosis genome predicted that a particular branch of the family tree would likely become drug resistant, and then validated their findings in an independent global tuberculosis data set.
“We’re running out of options in antibiotics and the options we have are often toxic – we have to get smarter at using what we have to prevent drug resistance,” said Dr Louis Grandjean, senior author of the study. “This is the first example of showing that we can get ahead of drug resistance. That will allow us in the future to use the pathogen genome to select the best treatments.”
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