Antibiotic tolerance facilitates the evolution of resistance

By Irit Levin-Reisman, Irine Ronin, Orit Gefen, Ilan Braniss, N. Shoresh, Nathalie Q. Balaban. Science, 2017

1,086 citations recorded by the source corpus.

Resistance on a background of tolerance Bacteria survive antibiotic exposure either because they are quiescent when antibiotics are around in the highest concentrations (i.e., tolerance) or because they acquire active biochemical resistance mechanisms (i.e., resistance). Both tolerance and resistance involve the acquisition of mutations from the wild type. Levin-Reisman et al. used in vitro evolution experiments to show that populations of bacteria that become genetically resistant to the antibiotic ampicillin most quickly do so on a background of tolerance mutations (see the Perspective by Lewis and Shan). Because the probability of a tolerant organism surviving is higher, it has a greater chance of subsequently acquiring resistance mutations. Tolerance is often overlooked in the clinic but should in future be screened for and targeted more precisely to reduce the rates of acquired resistance. Science, this issue p. 826; see also p. 796 Tolerance to antibiotics is often overlooked in the clinic, but tolerance drives the rapid evolution of resistance. Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been shown to lead rapidly to the evolution of tolerance—that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear. Here we used in vitro evolution experiments to explore this question. We found that in all cases, tolerance preceded resistance. A mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population. Thus, tolerance mutations pave the way for the rapid subsequent evolution of resistance. Preventing the evolution of tolerance may offer a new strategy for delaying the emergence of resistance.

Subfields: Genetics, Molecular Medicine

View Paper: https://www.semanticscholar.org/paper/bf4536609eb38193fac6c5c3e653f8a93c9a704a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. M. Huemer
2. S. Brugger
3. Annelies S. Zinkernagel
4. B. Bassler
5. Srikanth Mairpady Shambat
6. Brian K. Hammer

In Molecular Medicine

1. M. Huemer
2. S. Brugger
3. Annelies S. Zinkernagel
4. B. Bassler
5. Srikanth Mairpady Shambat

Citations in the corpus

• Antibiotic resistance and persistence—Implications for human health and treatment perspectives (2020, positive): “By using in vitro experiments and mathematical modelling, Balaban and co-workers recently showed that tolerance can precede resistance and that tolerance mutations can lead to a rapid evolution of antibiotic resistance (Levin-Reisman et al , 2017; Windels et al , 2019).”
• Surviving as a community: antibiotic tolerance and persistence in bacterial biofilms (2019, background): “coli strains isolated at the end of the experiment all arose from ancestral, tolerant strains (Figure 3A) (Levin-Reisman et al., 2017).”