Personalized antibiotic treatment strategies for tuberculosis sufferers
05.09.2022 12:58
With an estimated 1.4 million deaths and ten million cases annually, tuberculosis is one of the most common causes of death worldwide. Resistant and multidrug-resistant (MDR) variants of the tuberculosis pathogen Mycobacterium tuberculosis pose a major threat to tuberculosis control and global health. Mutations in the genome of M. tuberculosis bacteria that are linked to antibiotic resistance occur in MDR tuberculosis patient: inside in different combinations. In order to be able to treat sick people in a targeted manner and to successfully contain the transmission of antibiotic-resistant tuberculosis bacteria, the rapid recognition of these patient-specific resistance patterns is therefore crucial. With an international study published in the journal Lancet Microbe, DZIF researchers have now come a big step closer to this goal.
In the multicenter observational study, DZIF scientists from the Borstel Research Center and Heidelberg University Hospital sequenced the genomes of a large number of clinical patients M. tuberculosis-Isolates from all over the world. The researchers found that certain changes (mutations) in the bacterial genome were closely correlated with the effectiveness of antibiotics in the tuberculosis sufferers in question. The identification of certain mutations in the bacterial genome potentially makes it possible to predict which antibiotics will still work in a patient or whether the dose should be increased. With this knowledge, the success of the initial antibiotic therapy can be increased and further transmission of the pathogen can be prevented.
“This large-scale study is the result of close collaboration between DZIF scientists in Borstel and Heidelberg, the global diagnostics alliance FIND, and partners in five countries where tuberculosis is highly endemic. “Sequence analysis enables us to better understand the genetic basis of resistance to tuberculosis drugs and therefore enable faster, personalized tuberculosis treatment,” summarizes PD Dr. Claudia Denkinger, last author of the publication.
“In the comparative genomic analysis, for example, we also observed changes in the bacterial genome that do not always lead to clear results in classic resistance testing based on bacterial cultures, but can potentially influence therapy,” says Dr. Matthias Merker, one of the first authors of the study and Schleswig-Holstein Excellence Chair junior group leader at the Borstel Research Center.
“Our study also shows that the genetic analysis of the bacteria already enables a precise prediction of resistance to important tuberculosis antibiotics and can replace many of the classic and often lengthy tests,” adds Prof. Stefan Niemann from the National Reference Center for Mycobacteria in Borstel, one of the Last authors of the study. “In the future, we want to further expand this bacterial genome analysis technology, especially in the tuberculosis hot spots in southern Africa, Eastern Europe and Central Asia.”
The work was supported by the Bill & Melinda Gates Foundation, the German Center for Infection Research (DZIF) and the Schleswig-Holstein Cluster of Excellence “Precision Medicine for Chronic Inflammatory Diseases”.