Evolution of Drug-Resistant Bacteria Never Exposed to Antibiotics
Antibiotic-resistant microbes are a huge problem in human and global health. One of the microbial characteristics that allows development of resistant mutations is the short generational time and the large numbers of microorganisms that inhabit a particular niche. Large populations can accumulate a small proportion of individuals with mutations in random genes, and these random mutations generally must confer a benefit to the microbe to be maintained within the population. The common understanding is that drug-resistance mutations require drug exposure to be established. However, a new Antimicrobial Agents and Chemotherapy study reports evolution of drug-resistance mutations in bacteria that were never exposed to drugs.
AACJournal: Evolution of antibiotic resistance without antibiotic exposure
In this study, the researchers passaged Escherichia coli or Salmonella enterica in one of four different growth media without antibiotics for 500-1000 generations (roughly 1-2 weeks). The passaged cells were tested for growth with ten different antibiotics and compared to growth of the progenitor wild-type (wt) strain with that same antibiotic (see figure below). 520 different lineages of the two species were tested in total. Of these, 18 showed increased resistance to at least one drug, and 3 showed increased susceptibility.
First author Anna Knöppel and lead scientist Dan Andersson sequenced the bacterial lineages to look for resistance-associated mutations. Several mutations were identified in genes well established to be associated with drug resistance (see table below). The genomes of the less-susceptible lineages had multiple mutations, so it’s hard to pinpoint the exact mutations responsible, thought the scientists have good candidates to explore in future studies.
Development of resistance through genome mutation isn’t a surprise; microorganisms produce antimicrobial molecules to compete with their neighbors in natural habitats such as the soil. It’s also previously been shown that selection for growth in a stressful environment – such as in the presence of certain cleaning agents – can select for the mutations that also affect drug resistance. The new finding here is the evolution and fixation of some of these drug-resistant mutations in populations not experiencing any specific stress. These monoculture lineages were growing in relatively rich medium without obvious selection forces for the observed mutations.
What does this mean for human health? These results imply that resistance can arise and be found in bacterial populations based on their growth under natural conditions. This strengthens the call for discriminatory antibiotic use to keep these populations from expanding their niche. This basic research finding demonstrates the importance of stewardship in all cases, because we never know where resistance may stem from: transmission of already-resistant strains or selection for newly adapted strains in the absence of antibiotic use.