2014
DOI: 10.1016/j.cell.2014.01.068
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Antibiotic-Induced Replication Stress Triggers Bacterial Competence by Increasing Gene Dosage near the Origin

Abstract: Streptococcus pneumoniae (pneumococcus) kills nearly 1 million children annually, and the emergence of antibiotic-resistant strains poses a serious threat to human health. Because pneumococci can take up DNA from their environment by a process called competence, genes associated with antibiotic resistance can rapidly spread. Remarkably, competence is activated in response to several antibiotics. Here, we demonstrate that antibiotics targeting DNA replication cause an increase in the copy number of genes proxim… Show more

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Cited by 223 publications
(347 citation statements)
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References 70 publications
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“…The increase in gene dosage is sufficient to trigger the competent state (137). The origin-proximal location of early com genes thus constitutes a sensory mechanism that enables cells to activate competence in response to antibiotics interfering with DNA replication (137). In contrast, the SOS response mediated by HdiR and competence are antagonistic processes in S. thermophilus (138).…”
Section: The Sos Response In Lab: Dna As a Sensormentioning
confidence: 99%
See 2 more Smart Citations
“…The increase in gene dosage is sufficient to trigger the competent state (137). The origin-proximal location of early com genes thus constitutes a sensory mechanism that enables cells to activate competence in response to antibiotics interfering with DNA replication (137). In contrast, the SOS response mediated by HdiR and competence are antagonistic processes in S. thermophilus (138).…”
Section: The Sos Response In Lab: Dna As a Sensormentioning
confidence: 99%
“…This results in a higher copy number of genes close to the replication origin, including the comCDE operon. The increase in gene dosage is sufficient to trigger the competent state (137). The origin-proximal location of early com genes thus constitutes a sensory mechanism that enables cells to activate competence in response to antibiotics interfering with DNA replication (137).…”
Section: The Sos Response In Lab: Dna As a Sensormentioning
confidence: 99%
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“…Replication stress is defined here as the slowing of replication fork progression during DNA synthesis (Zeman and Cimprich 2014) which, in next-generation sequencing data, has been associated with a progressive, directional decrease in DNA copy number along the genome (Slager et al 2014). We therefore compared ptDNA coverage curves for each mutant line to the WT.…”
Section: U-turn-like Rearrangements Are Associated With Replication Smentioning
confidence: 99%
“…[15] A recent study revealed that antibiotics targeting DNA replication activate competence in Streptococcus pneumonia, which leads to increased uptake of foreign DNA. [16] AMCRA: Center of Expertise on Antimicrobial Consumption and Resistance in Animals in Belgium Mission, objectives, and achievements AMCRA, a Belgian initiative, was launched in January 2012. From the One World, One Health perspective, AMCRA proposes guidelines to direct the entire animal industry towards responsible and reduced antibiotic use, thereby limiting the selection and spread of antibiotic-resistant bacteria (www.amcra.be).…”
Section: Transfer Of Resistance and Environmental Resistance Reservoirmentioning
confidence: 99%