Elevated Mutagenesis Does Not Explain the Increased Frequency of Antibiotic Resistant Mutants in Starved Aging Colonies

Katz, Sophia; Hershberg, Ruth

doi:10.1371/journal.pgen.1003968

Cited by 28 publications

(43 citation statements)

References 34 publications

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“…We also observed a sharp increase in the frequency of resistance to a second antibiotic, nalidixic acid (Katz and Hershberg 2013). We then used whole-genome sequencing to show conclusively that increased mutagenesis could not explain the increased frequency of resistance observed to either of the two antibiotics (Katz and Hershberg 2013). Therefore, SIM cannot explain the Bjedov et al results, and these results cannot be seen as evidence of SIM occurring in natural bacterial populations.…”

Section: Bacterial Mutation As An Evolutionary Forcementioning

confidence: 81%

“…Consistent with their results, we were able to show a substantial increase in the frequency of resistance to rifampicin in aging colonies compared with young colonies. We also observed a sharp increase in the frequency of resistance to a second antibiotic, nalidixic acid (Katz and Hershberg 2013). We then used whole-genome sequencing to show conclusively that increased mutagenesis could not explain the increased frequency of resistance observed to either of the two antibiotics (Katz and Hershberg 2013).…”

Section: Bacterial Mutation As An Evolutionary Forcementioning

confidence: 93%

“…Modeling has shown that such stress-induced mutagenesis (SIM) should be highly beneficial (Ram and Hadany 2012), as it could allow bacteria to transiently increase mutagenesis particularly when they are most pressured to adapt. Yet, the study of SIM has been plagued by fierce debate (e.g., Slechta et al 2002Slechta et al , 2003Roth et al 2003Roth et al , 2006Wrande et al 2008;Katz and Hershberg 2013). In this review, I do not have sufficient space to delve into the full debate, but will only introduce some points of contention.…”

Section: Constitutive Mutators and Stress-induced Mutagenesismentioning

confidence: 94%

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Mutation—The Engine of Evolution: Studying Mutation and Its Role in the Evolution of Bacteria: Figure 1.

Hershberg

2015

Cold Spring Harb Perspect Biol

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Mutation is the engine of evolution in that it generates the genetic variation on which the evolutionary process depends. To understand the evolutionary process we must therefore characterize the rates and patterns of mutation. Starting with the seminal Luria and Delbruck fluctuation experiments in 1943, studies utilizing a variety of approaches have revealed much about mutation rates and patterns and about how these may vary between different bacterial strains and species along the chromosome and between different growth conditions. This work provides a critical overview of the results and conclusions drawn from these studies, of the debate surrounding some of these conclusions, and of the challenges faced when studying mutation and its role in bacterial evolution.G enetic variation is a prerequisite to evolutionary change. In the absence of such variation, no subsequent change can be achieved. Genetic variation is ultimately all generated by mutation. It is therefore clear that mutation is a major evolutionary force that must be studied and understood to understand evolution. Yet, often mutation is set aside and thought of as a random generator of variation that follows very simple and predictable rules. Many reviews of mutation deal with the molecular mechanisms of mutation and repair (e.g., Modrich 1991; Smith 1992; Lieber 2010). This work, in contrast, relates to mutation as an evolutionary force, focusing on bacteria. We will show that mutation is extremely difficult to study, that we do not know nearly enough about mutation and that recently several of our decades-old assumptions were shown to be mistaken, in light of newly available data. MUTATIONS VERSUS SUBSTITUTIONSIt is important to note that, in this article, we will only be considering de novo point mutations. We will not discuss large insertions or deletions or horizontal gene transfer events. To proceed, we must define some terms.For the purpose of this article, we will define "DNA mutations" as single nucleotide changes in the DNA sequence of an individual organism. These will be the end result of the molecular DNA change, and of the fact that this DNA change was not repaired by the cellular repair systems. Once a mutation occurs and is present within an individual, it will either increase in

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Section: Bacterial Mutation As An Evolutionary Forcementioning

confidence: 81%

Section: Bacterial Mutation As An Evolutionary Forcementioning

confidence: 93%

Section: Constitutive Mutators and Stress-induced Mutagenesismentioning

confidence: 94%

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Mutation—The Engine of Evolution: Studying Mutation and Its Role in the Evolution of Bacteria: Figure 1.

Hershberg

2015

Cold Spring Harb Perspect Biol

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“…Stress-induced mutagenesis (SIM)-the increase of mutation rates in stressed or maladapted individuals-has been demonstrated in several species, including both prokaryotes and eukaryotes [15]. SIM has been observed in laboratory strains [16,17] and natural populations of Escherichia coli [18] (but see [19]), and in other species of bacteria such as pseudomonads [20], Helicobacter pylori [21], Vibrio cholera [22] and Streptococcus pneumonia [23]. SIM has also been observed in yeast [24,25], algae [26], nematodes [27], flies [28] and human cancer cells [29].…”

Section: Introductionmentioning

confidence: 99%

Stress-induced mutagenesis and complex adaptation

Ram

Hadany

2014

Proc. R. Soc. B.

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Because mutations are mostly deleterious, mutation rates should be reduced by natural selection. However, mutations also provide the raw material for adaptation. Therefore, evolutionary theory suggests that the mutation rate must balance between adaptability-the ability to adapt-and adaptedness-the ability to remain adapted. We model an asexual population crossing a fitness valley and analyse the rate of complex adaptation with and without stress-induced mutagenesis (SIM)-the increase of mutation rates in response to stress or maladaptation. We show that SIM increases the rate of complex adaptation without reducing the population mean fitness, thus breaking the evolutionary trade-off between adaptability and adaptedness. Our theoretical results support the hypothesis that SIM promotes adaptation and provide quantitative predictions of the rate of complex adaptation with different mutational strategies.

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“…Particularly, the role of selection in increasing the frequency of drug-resistant mutants is contentious in studies like Bjedov et al (2003), which relied on aged, stressed colonies. This is because some mutants supposedly have a growth advantage in old colonies on agar plates (Katz and Hershberg 2013).…”

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confidence: 99%

Stress-Induced Mutation Rates Show a Sigmoidal and Saturable Increase Due to the RpoS Sigma Factor in Escherichia coli

Maharjan¹,

Ferenci

2014

Genetics

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Elevated Mutagenesis Does Not Explain the Increased Frequency of Antibiotic Resistant Mutants in Starved Aging Colonies

Cited by 28 publications

References 34 publications

Mutation—The Engine of Evolution: Studying Mutation and Its Role in the Evolution of Bacteria: Figure 1.

Mutation—The Engine of Evolution: Studying Mutation and Its Role in the Evolution of Bacteria: Figure 1.

Stress-induced mutagenesis and complex adaptation

Stress-Induced Mutation Rates Show a Sigmoidal and Saturable Increase Due to the RpoS Sigma Factor in Escherichia coli

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