Tuberculosis is a serious infectious disease transmitted by bacteria. According to the World Health Organization, the disease killed 1.5 million people in 2014, making it one of the deadliest infectious diseases in the world. Antibiotics can be used to treat the disease but treatment can be difficult. Different populations of mycobacteria have varying levels of antibiotic tolerance. Even when the mycobacteria are from the same colony, sharing a common genetic background, individual bacteria will respond differently to treatment. New research, just published in the journal Proceedings of the National Academy of Sciences, finally provides some insight as to why some bacteria respond differently to antibiotics when compared to other bacteria in the same colony.
Researchers from the Tufts University School of Medicine designed an experiment to investigate what factors allowed some bacteria to respond differently to antibiotic treatments. Previous research had showed that mycobacteria divide asymmetrically during reproduction. This leads to differently sized daughter cells with the smaller one generally growing at a slower rate. The researchers speculated that this could potentially explain some of the differences in bacterial resistance.
The team of scientists studied Mycobacterium smegmatis, a harmless relative of Mycobacterium tuberculosis. They tested the bacteria’s resistance to a commonly used antibiotic called rifampicin. In addition to studying living cells using microscopy and imaging tools, the researchers incorporated mathematical models into their work. They found that bacteria vulnerability to antibiotics was mostly dependent on the cell’s current stage of the cell cycle. Bacteria at the beginning or the very end of the cell cycle were the most sensitive to rifampicin. Mid-sized bacteria in the middle of their cell cycles were the most resistant to the antibiotic.
These findings show that small differences in the current size and cell cycle stage of an individual mycobacterium can change how that particular bacterium responds to antibiotics. The authors believe that by understanding the factors that affect antibiotic sensitivity, we can develop more efficient drugs for treating tuberculosis and related diseases.
Kirill Richardson et al. Temporal and intrinsic factors of rifampicin tolerance in mycobacteria. Proceedings of the National Academy of Sciences (2016).