Bacterial gene amplification: implications for the evolution of antibiotic resistance

Sandegren, Linus; Andersson, Dan I.

doi:10.1038/nrmicro2174

Cited by 293 publications

(293 citation statements)

References 122 publications

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“…It is plausible that the duplications of emrE may compensate for the expression decrease upon norfloxacin treatment, but knocking out or overexpressing emrE in E. coli in previous studies did not elicit norfloxacin resistance change (59,60). Thus, the decrease in emrE expression may just be a coincidence, although there are numerous known cases of gene duplication/amplification related to the development of antibiotic resistance (61).…”

Section: Coincidence Of Is5-mediated Duplications and Emre Efflux Pummentioning

confidence: 97%

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Long

Miller

Strauss

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

143

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Although it is well known that microbial populations can respond adaptively to challenges from antibiotics, empirical difficulties in distinguishing the roles of de novo mutation and natural selection have left several issues unresolved. Here, we explore the mutational properties of Escherichia coli exposed to long-term sublethal levels of the antibiotic norfloxacin, using a mutation accumulation design combined with whole-genome sequencing of replicate lines. The genome-wide mutation rate significantly increases with norfloxacin concentration. This response is associated with enhanced expression of error-prone DNA polymerases and may also involve indirect effects of norfloxacin on DNA mismatch and oxidative-damage repair. Moreover, we find that acquisition of antibiotic resistance can be enhanced solely by accelerated mutagenesis, i.e., without direct involvement of selection. Our results suggest that antibiotics may generally enhance the mutation rates of target cells, thereby accelerating the rate of adaptation not only to the antibiotic itself but to additional challenges faced by invasive pathogens.antibiotic resistance | mutation rate | resistance evolution | DNA repair | low-fidelity polymerases

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Section: Coincidence Of Is5-mediated Duplications and Emre Efflux Pummentioning

confidence: 97%

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Long

Miller

Strauss

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

184

143

View full text Add to dashboard Cite

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“…The phenotypes caused by duplications can be detected by selection and contribute to fitness whenever growth is limited by quantity or activity of a particular protein (Sonti and Roth 1989;Tlsty et al 1989;Andersson et al 1998). Selected increases in gene copy number can enhance the likelihood of point mutations that further increase fitness by providing more targets for change Sandegren and Andersson 2009;Sun et al 2009).…”

mentioning

confidence: 99%

Duplication Frequency in a Population of Salmonella enterica Rapidly Approaches Steady State With or Without Recombination

Reams¹,

Kofoid²,

et al. 2010

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Tandem duplications are among the most common mutation events. The high loss rate of duplication suggested that the frequency of duplications in a bacterial population (1/1000) might reflect a steady state dictated by relative rates of formation (k F ) and loss (k L ). This possibility was tested for three genetic loci. Without homologous recombination (RecA), duplication loss rate dropped essentially to zero, but formation rate decreased only slightly and a steady state was still reached rapidly. Under all conditions, steady state was reached faster than predicted by formation and loss rates alone. A major factor in determining steady state proved to be the fitness cost, which can exceed 40% for some genomic regions. Depending on the region tested, duplications reached 40-98% of the steady-state frequency within 30 generations-approximately the growth required for a single cell to produce a saturated overnight culture or form a large colony on solid medium (10 9 cells). Long-term bacterial populations are stably polymorphic for duplications of every region of their genome. These polymorphisms contribute to rapid genetic adaptation by providing frequent preexisting mutations that are beneficial whenever imposed selection favors increases in some gene activity. While the reported results were obtained with the bacterium Salmonella enterica, the genetic implications seem likely to be of broader biological relevance.

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“…see Schrag and Perrot, 1996;Björkman et al, 2000). Gene amplification enables bacteria to increase the level of resistance to antibiotics without acquiring new or modifying existing structural genes (see Sandegren and Andersson, 2009 for an excellent review). Moreover, amplifications increase the mutational targets of these genetic regions, thereby increasing the likelihood of an adaptive change in these structural genes (Sun et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Adjusting to alien genes

Johnsen

Levin

2010

Molecular Microbiology

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SummaryFrom the perspective of a bacterium, higher eukaryotes are oversexed, unadventurous and reproduce in an inconvenient way. Sex, or recombination following horizontal gene transfer (HGT) events, to be less provocative, is a rare event for a bacterium, but a potentially profound one. Through HGT a bacterium can acquire DNA from distant as well as closely related species and, thereby, instantly obtain genes that encode novel functions or replace its existing genes with better ones. While there is an abundance of retrospective evidence for HGT in bacteria, there has been little consideration of the dynamics of the process. In this issue of Molecular Microbiology Lind et al. explore these dynamics theoretically, and then experimentally by substituting Salmonella Typhimurium ribosomal genes with orthologues from various microbial origins. The authors show that the majority of these newly acquired ribosomal proteins reduce fitness in S. Typhimurium, but within short order (40-250 generations) subsequent evolution will mitigate the fitness costs of the alien alleles. The presented results suggest that that at least the initial phase of adapting to alien genes of this informational core ilk is not by changing them but rather by increasing their level of expression by gene amplification. Lind et al. argue that their results provide an explanation as to why duplicated genes are overrepresented among horizontally transferred genes. Do we believe in evolution? Believe in it? We've seen it, as has everybody else with the good taste to do research with bacteria. Indeed, even the more intelligently designed Creationists accept the kind of evolution we see.Small changes in the genetic composition of populations over relatively short periods of time, so-called microevolutionary events, are readily observed, whether we want to see them or not. But, what about evolutionary events that occurred before we appeared on the scene; can we do more than just make up stories about the genetic and ecological (selection) processes responsible and illustrate them with equations and sequences of As, Ts, Cs and Gs extracted from extant or very recently extinct organisms? The answer is yes. With bacteria that can be cultured in the lab, we can do experiments to test evolutionary hypotheses. To be sure, evidence gathered in this way only supports or refutes the evolutionary hypotheses being tested, but that's all that Science (inductive inference, if you prefer) can do anyhow. We cannot say with absolute assurance that's how evolution proceeded, and couldn't even if we were eyewitnesses to that evolution.The study by Lind et al. (2010) in this issue off Molecular Microbiology addresses the evolutionary

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Bacterial gene amplification: implications for the evolution of antibiotic resistance

Cited by 293 publications

References 122 publications

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Antibiotic treatment enhances the genome-wide mutation rate of target cells

Duplication Frequency in a Population of Salmonella enterica Rapidly Approaches Steady State With or Without Recombination

Adjusting to alien genes

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