TB research boosted by sequenced strains

Image: CDC/ James Archer

Image: CDC/ James Archer

Scientists working with tuberculosis (TB) have recently been given a boost in the quest to develop better treatments for TB. They now have access to over 100 strains that have been genome sequenced, including strains resistant to the major TB drugs.

The study, reported in the journal BMC Medicine, was led by the London School of Hygiene & Tropical Medicine. The 144 strains of TB bacteria sequenced are part of a bank of samples held at the Institute of Tropical Medicine in Antwerp (ITM), Belgium. The strains are available on request and will allow scientists to investigate drug resistance mechanisms and could bring new drugs a step closer.

Tuberculosis is a leading cause of death worldwide killing 1.5 million people each year, including 140,000 children. It is an airborne disease caused by a bacterium (Mycobacterium tuberculosis) and the World Health Organization estimate that there are nine million news cases every year and that one third of the world’s population has been latently infected and is at risk of developing the disease at some time in the future. Attempts to control the disease are hampered by the lack of an effective vaccine and the emergence strains of bacteria that are resistant to multiple drugs.

Taane Clark, Professor of Genomics and Global Health at the School who led the analysis, said: “Combating the rise of drug resistant tuberculosis is one of the most pressing public health challenges facing the world today. Using a genome-wide approach, we have identified genetic markers underlying drug resistance, and by modelling protein structures now understand the impact of these mutations on drug resistance mechanisms. This approach could pave the way for identifying secondline and new drug resistance mutations.”

The samples were collected as part of a World Health Organisation initiative to stimulate and accelerate research towards understanding the bacteria (Mycobacterium tuberculosis). Working in collaboration with the Mycobacteriology Unit in Belgium they collected and characterised bacteria isolated from patients from around the world.

The Belgian Coordinated Collections of Microorganisms at the ITM has been operational since the 1st of February 2011. It harbours one of the largest and most diverse collections of well-documented mycobacteria worldwide, including the TDR TB-Strain bank.

Dr. Leen Rigouts from ITM said: “We are thrilled that we can now provide whole genome data for these strains, as it will assist with answering important biological questions about TB.”

Dr. Ruth McNerney who co-initiated the project and now works at the University of Cape Town in South Africa where TB is the number one killer, said: “This is a great resource, working together and sharing knowledge is surely the best way to defeat this terrible disease.”

Ongoing work is combining these data with others sourced globally in an attempt to identify additional markers of resistance, particularly to second-line drugs where genetic mechanisms are poorly understood.

Publication:       

Phelan J et al. Mycobacterium tuberculosis whole genome sequencing and protein structure modelling provides insights into anti-tuberculosis drug resistance. BMC Medicine 2016;

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