The Rise of Extensively Drug Resistant Tuberculosis
Tuberculosis, once known as consumption, has plagued humanity since time immemorial. It is caused by Mycobacterium tuberculosis bacilli, which are transmitted from person to person through the air. Prior to modern medicine, there was no effective treatment for the disease, and TB patients would invariably waste away as the bacterium slowly destroyed their lungs and other body systems. While artists and novelists have often romanticized these pale sufferers and depicted consumption as a peaceful, noble death, tuberculosis is actually a gruesome disease that causes severe pain and suffering.
Fortunately, modern medicine has given us drugs such as isoniazid, rifampicin, ethambutol, and pyrazinamide. Lengthy regimens of these antibiotics are often effective at curing tuberculosis, yet the use of these antibiotics comes with a tradeoff: certain strains of the targeted bacterium have gradually accumulated mutations that enable them to survive exposure to many common drugs. Each newly acquired resistance gene is an evolutionary advantage for the bacterium, so resistant strains tend to proliferate when the infection spreads to other people.
As a result of these mutations, two particularly dangerous modern forms of the disease have arisen: multi-drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). While these can sometimes be cured by intense treatment regimens (often lasting years, costing hundreds of thousands of dollars, and producing numerous unpleasant side effects), their frequent lethality makes them a serious global health concern.
A group of researchers has recently traced the evolution of extensively drug resistant tuberculosis in the European and Russian populations of drug-resistant M. tuberculosis (these populations are collectively known as the W148 clade). Using hundreds of samples collected from throughout Europe between 1995 and 2013, the researchers performed an exhaustive genetic analysis of single-nucleotide polymorphisms (SNPs). SNPs are minor variations in the genetic code resulting from mutations that change one nucleotide to another. These variations are passed on to offspring, and since they typically have no effect on an organism’s phenotype, natural selection neither favors nor disfavors them. Analysis of the unique combination of SNPs that has accumulated over time in the genome of an individual strain of bacteria can reveal its evolutionary relationship to other strains of the same species.
The researchers used the results to compile a cladogram which showed the evolutionary descent of the modern strains of drug-resistant TB. From this diagram, it was evident that the many TB strains in the W148 clade are all descended from a common ancestor that arose around 1963. This common ancestor possessed resistance to just two antibiotics: isoniazid and streptomycin. When the researchers assessed the extent of resistance present in the W148 clade, they found an alarming degree of resistance to both first-line drugs (which are considered the most effective treatments) and second-line drugs (which are less effective and have more serious side effects).
As the researchers observed, the spread of drug-resistant Russian strains of TB in the late twentieth century was associated with the fall of the USSR. As former Soviet citizens migrated westward, two consecutive TB epidemics in the 1980s and 90s spread antibiotic resistance to Western Europe and beyond. Due to deficiencies in TB treatment during those times of economic upheaval, new mutations accumulated rapidly, causing drug-resistant strains to become prolific. This laid the foundation for the development of modern MDR-TB and XDR-TB.
The continued increases in drug resistance within the W148 clade do not bode well for the future. While antibiotic-resistant tuberculosis is not as transmissible as SARS-CoV2 (and thus unlikely to cause a global pandemic), it is far more deadly to those it infects. Unless new antibiotics are developed, TB may once again become the untreatable “white plague” that tormented past generations and continues to be a scourge in developing nations today.
If you are interested in reading more research on this topic, you can find similar research in Frontiers in Cellular and Infection Microbiology.
Grove City College students can find any of these journals by simply searching the journal name in Discover on the Henry Buhl Library’s homepage. And don’t forget— if you’d like to find more related resources, the library maintains a list of A-Z Databases with an entire tab dedicated to biology!
