It is well known that low concentrations of antibiotics can cause resistance to evolve among bacteria. Now, a group of researchers from IISER Pune has taken this further to explore how exactly this happens.
They have studied how resistance to the antibiotic rifampicin evolves in E. coli under two conditions — when the antibiotic is present in low or high concentrations, and when there is steady or pulsed supply of antibiotics.
- Bacteria develop drug resistance both when they are within the body and outside. The fact that antibiotics are unevenly distributed within the body or intake of drugs could be stopped midway can lead to evolution of drug resistance.
- Similarly, low doses of such drugs available intermittently in the environment can also cause drug resistance to evolve in the bacteria.
- According to a study published in the journal Genetics, the process of evolution of drug resistance appears to be rapid. We found that E. coli can evolve resistance to rifampicin within a few generations of drug exposure.
- A characteristic of some drug-resistant strains of bacteria is that they do not live in isolation but get connected to each other, forming biofilms.
- Using genetics and biochemistry, the researchers found that when under exposure to low concentrations of rifampicin, the E. coli tend to form biofilms.
- This did not happen when they were exposed to high concentrations of antibiotic. This is pretty dangerous since biofilms by themselves are a major challenge for hospitals and clinicians.
- Many genetic changes in the E.coli descendents were observed when the bacteria were exposed to low concentration of the antibiotic rifampicin.
- In order to understand the relevant genetic mutations that helped the bacteria form biofilms, the researchers engineered the individual mutations into the parent bacteria and studied which particular mutation was responsible for resistance against rifampicin.
- They found that biolfilm formation was mediated by the activation of particular gene called the fim operon promoter. Activation of the gene allowed the expression of a type of fimbriae — thread-like structures that help a bacterium attach itself to another bacterium. These are important in the formation of biofilms.
- Though the researchers have specifically studied how E. coli evolve resistance against rifampicin, the results may be extrapolated to Gram-negative bacteria in general. This will be useful in studying drug resistance in other Gram-negative bacteria such as Klebsiella and Salmonella which cause hazardous infections.
- However, the team is planning to extend this study to a host of other antibiotics. Eventually, we aim to generate a multi-antibiotic low and high drug concentration genetic map that will point out significant genes and cellular pathways that are responsible for the evolution of resistance at low and high drug respectively.