Side effects of antibiotics on genetic variability

Abstract

In recent years, there has been accumulating evidence that antibiotics, besides their antimicrobial action, potentially have a number of undesired side effects that can, at least in some cases, promote genetic variability of bacteria. In addition to resistant variants, antibiotics have also been shown to select mutator clones, thus stimulating evolution towards further resistance. Furthermore, mutations, recombination and horizontal gene transfer have been reported to be somehow affected when bacteria are exposed to subinhibitory concentrations of certain antibiotics. These findings may have implications for the use of antibiotics, because they may have undesired side effects, such as enhancing antibiotic resistance evolution. Here we present data supporting (or not) this fearsome possibility and discuss whether this potential threat should be taken into consideration.

Tempo and Mode of Plant RNA Virus Escape from RNA Interference-Mediated Resistance

“…In the second case we found that these populations accumulated escape mutations at a much higher frequency and, therefore, were able to successfully infect the fully resistant hosts at earlier times in virus evolution. The second result was highly predictable, since it recapitulates the evolution of bacteria at antibiotic concentrations below the MIC (14) and has been solidly established. At subinhibitory concentrations of the antiviral amiR, mutant genotypes gain a fitness advantage, given their ability to replicate despite the presence of the antiviral amiR, whereas wild-type genomes may still suffer from the inhibitory effects.…”

Integrons: Past, Present, and Future

“…Continued exposure to variable, subinhibitory levels of selective agents creates a circumstance where lineages with higher rates of genetic change have an advantage (254,255). Thus, an unintended consequence of the antibiotic revolution might be the fixation of bacterial lineages with inherently higher basal rates of mutation, recombination, and lateral gene transfer (153,175).…”

Modulation of Salmonella gene expression by subinhibitory concentrations of quinolones

“…38 It is well-established that antimicrobial/antibacterial pressure can select for either resistant cells or cells with an increased mutation/recombination rate, permanently becoming hypermutators. 39 Our studies indicate that the older as well as newer FQs, such as moxifloxacin, levofloxacin and gatifloxacin, strongly induce transient mutagenic mechanisms such as the SOS response. The multiple effects, mutagenic and otherwise, of sub-MIC FQs can be explained by the predominant activity of FQs as activators of stress response.…”

“…16,38,39 These effects include increased mutagenicity (transient), 39 phage induction and its sequelae (virulence), enhanced adhesion, integron cassette recombination 40 and others. 38 It is well-established that antimicrobial/antibacterial pressure can select for either resistant cells or cells with an increased mutation/recombination rate, permanently becoming hypermutators.…”