The trade-off to antibiotic resistance
When bacteria evolve resistance to one antibiotic, they may become more sensitive to another depending on a set of previously unknown factors.
Over time bacteria can undergo a number of genetic mutations that allow them to evolve in response to changes in their surrounding environment. This process of ‘bacterial evolution’ is one of the major causes of antibiotics resistance, whereby disease-causing microorganisms become resistant to multiple drugs and can no longer be destroyed using antibiotic treatment. However, when bacteria become resistant to a drug this can result in an evolutionary trade-off known as ‘collateral sensitivity’ — when evolving resistance to one drug causes bacteria to gain increased sensitivity to another.
Now, Barbosa, Roemhild et al. have investigated whether this evolutionary trade-off could be exploited to tackle the antibiotic crisis and prevent bacteria adapting to different treatments. If this evolutionary trade-off is to be used medically, it must be stable long enough for the bacteria population to either become extinct, or less able to evolve multi-drug resistance. To test how stable collateral sensitivity is over time, Barbosa, Roemhild et al. studied the bacterium Pseudomonas aeruginosa which is known to evolve collateral sensitivity to certain drug treatments.
P. aeruginosa were subjected to two rounds of evolution: first, bacteria were evolved to resist ‘Drug A’ and at the same time became more sensitive to another drug, ‘Drug B’. The bacteria were then allowed to adapt to Drug B either alone or in the presence of Drug A. These evolutionary experiments revealed that the following factors affected the stability of the trade-off: the molecular structure of the antibiotic bacteria evolved sensitivity to, the strength of the original evolutionary trade-off (i.e. how sensitive bacteria became), the order drugs were administrated, and whether resistance came at a large fitness cost (i.e. when the genetic mutations promoting resistance affect bacteria’s ability to replicate and survive in normal conditions).
According to the World Health Organization, P. aeruginosa is the second most problematic multi-drug resistant bacteria. The data collected in this study could therefore be used to develop a new antibiotic therapeutic strategy for fighting this bacterium, as well as other microbes which are resistant to multiple drugs.
Originally published at https://elifesciences.org/digests/51481.
