doi:10.1038/nindia.2014.159 Published online 24 November 2014
Sub-lethal concentrations of antibiotics allow bacteria to become resistant very quickly, a new study says1. It also notes that lower the concentration of the antibiotic, quicker the resistance evolves.
Working with a common laboratory antibiotic kanamycin (not used for prescription purposes) and the bacterium Escherichia coli, a group of scientists at the National Centre for Biological Sciences (NCBS), Bangalore, were trying to understand the process of evolution of antibiotic resistance. “There exists a trade-off in bacteria between acquiring resistance and staying fit. Since antibiotics usually attack key biological processes, it is likely that in the process of acquiring resistance the bacteria becomes unfit,"says Aswin Sai Narain Seshasayee, lead author of the study.
The key for bacteria is to acquire a resistance mechanism that does not compromise its fitness, and also provides resistance to antibiotics, he says.
The scientists exposed E. coli to two sub-lethal concentrations of kanamycin: 4 µg/ml and 8 µg/ml. They found that, growth in 4 µg/ml kanamycin quickly resulted in a population of bacteria that were not only resistant to the antibiotic but also displayed little defect in growth in the absence of the antibiotic. On the other hand, 8 µg/ml kanamycin showed persistence of many sick but resistant mutants for much longer.
“The lower concentrations are interesting because they are very similar to situations when people don't comply with their antibiotic prescriptions and skip doses or when traces of antibiotics are found in edible products,"Seshasayee says. It is easier for bugs to acquire resistance in the natural environment since they are acquired not just by mutation but also by lateral transfer from one bacterium to another.
The team sequenced genomes of many of the resistant bacteria to identify mutations. They differentiated the DNA sequence changes in the fit mutants from those in the sick variants. They also identified a variety of secondary mutations.
1. Mogre, A. et al. Genomic analysis reveals distinct concentration-dependent evolutionary trajectories for antibiotic resistance in Escherichia coli. DNA Res. (2014) doi: 10.1093/dnares/dsu032