Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus

Alves, Ingrid Reale; Lima-Noronha, Marco A.; Silva, Larissa G.; Fernández-Silva, Frank S.; Freitas, Aline Luiza D.; Marques, Marilis V.; Galhardo, Rodrigo S.

doi:10.1016/j.dnarep.2017.09.003

Cited by 20 publications

(24 citation statements)

References 41 publications

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“…However, recent studies have shown the emergence of de novo mutations, after the exposure of bacteria in non-lethal stress conditions [8]. This event is known as “adaptative resistance” [9,10], and it is related to the triggering of the SOS system, which leads to increased rates of recombination and mutation, affecting the evolution and dissemination of bacterial resistance [11,12]. This event is known as “adaptative resistance” [9,10], and it is related to the triggering of the SOS system, which leads to increased rates of recombination and mutation, affecting the evolution and dissemination of bacterial resistance [11,12].…”

Section: Introductionmentioning

confidence: 99%

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus

et al. 2019

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The occurrence of damage on bacterial DNA (mediated by antibiotics, for example) is intimately associated with the activation of the SOS system. This pathway is related to the development of mutations that might result in the acquisition and spread of resistance and virulence factors. The inhibition of the SOS response has been highlighted as an emerging resource, in order to reduce the emergence of drug resistance and tolerance. Herein, we evaluated the ability of betulinic acid (BA), a plant-derived triterpenoid, to reduce the activation of the SOS response and its associated phenotypic alterations, induced by ciprofloxacin in Staphylococcus aureus. BA did not show antimicrobial activity against S. aureus (MIC > 5000 µg/mL), however, it (at 100 and 200 µg/mL) was able to reduce the expression of recA induced by ciprofloxacin. This effect was accompanied by an enhancement of the ciprofloxacin antimicrobial action and reduction of S. aureus cell volume (as seen by flow cytometry and fluorescence microscopy). BA could also increase the hyperpolarization of the S. aureus membrane, related to the ciprofloxacin action. Furthermore, BA inhibited the progress of tolerance and the mutagenesis induced by this drug. Taken together, these findings indicate that the betulinic acid is a promising lead molecule in the development helper drugs. These compounds may be able to reduce the S. aureus mutagenicity associated with antibiotic therapies.

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Section: Introductionmentioning

confidence: 99%

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus

et al. 2019

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“…It has been reported that ImuB and ImuC act cooperatively during TLS in several bacterial species (Boshoff et al ; Le Chatelier et al ; Galhardo et al ; Warner et al ; Alves et al ). Based on sequence analyses, Warner et al () suggested that ImuB is devoid of DNA polymerase activity because it lacks the highly conserved residues of the active site required to polymerize DNA.…”

Section: Discussionmentioning

confidence: 99%

ImuB and ImuC contribute to UV‐induced mutagenesis as part of the SOS regulon in Pseudomonas aeruginosa

Luján

Moyano

Martino

et al. 2019

Environ and Mol Mutagen

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DNA damage‐induced mutagenesis is a process governed by the SOS system that requires the activity of specialized DNA polymerases. These polymerases, which are devoid of proof‐reading activity, serve to increase the probability of survival under stressful conditions in exchange for an error‐prone DNA synthesis. As an opportunistic pathogen of humans, Pseudomonas aeruginosa employs adaptive responses that originally evolved for survival in many diverse and often stressful environmental conditions, where the action of error‐prone DNA polymerases may be crucial. In this study, we have investigated the role of the polymerases ImuB and ImuC in P. aeruginosa DNA‐damage induced mutagenesis. UV irradiation of imuB‐ and imuC‐deletion mutants showed that both genes contribute to UV‐induced mutagenesis in this bacterium. Furthermore, we confirmed that UV treatment significantly increase the expression levels of the imuB and imuC genes and that they are co‐transcribed as a single transcriptional unit under the control of LexA as part of the SOS regulon in P. aeruginosa. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

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“…Compared with Pol II and Pol IV, Pol V catalyzes DNA synthesis with the lowest fidelity and is the main enzyme for bacterial SOS-induced mutations (Fuchs et al, 2004;Goodman & Woodgate, 2013;Jaszczur et al, 2016). However, only approximately one third (1,707 strains) of the sequenced bacteria (5,360 strains, KEGG data in Jan 2020) encodes Pol V. In those strains without Pol V, nearly a half (1,699 strains) contains DnaE2 (ImuC in some publications) protein that has been shown to play a key role in SOS mutagenesis (Abella et al, 2004;Alves et al, 2017;Baker & Kornberg, 1998;Boshoff et al, 2003;Erill et al, 2006;Galhardo et al, 2005;Tsai et al, 2012;Timinskas et al, 2014;Warner et al, 2010). DnaE2 is a structural homolog of DnaE1 subunit of replicative DNA polymerase III.…”

Section: E Coli Contains Three Different Tls Polymerases Pol II (Pomentioning

confidence: 99%

“…The imuA and imuB genes, usually located in the SOS-regulated operon of imuA-imuB-dnaE2, are required for DnaE2 mutagenesis (Abella et al, 2004;Alves et al, 2017;Erill et al, 2006;Galhardo et al, 2005). The imuA or imuB mutants of Caulobacter crescentus and Mycobacterium tuberculosis showed a significant reduction in SOS-induced mutation frequency, similar to that of the dnaE2 mutants (Galhardo et al, 2005;Warner et al, 2010).…”

Section: E Coli Contains Three Different Tls Polymerases Pol II (Pomentioning

confidence: 99%

ImuA participates in SOS mutagenesis by interacting with RecA1 and ImuB inMyxococcus xanthus

Sheng

Wang

Jiang

et al. 2020

Preprint

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Bacteria have two pathways to restart stalled replication forks caused by environmental stresses, error-prone translesion DNA synthesis (TLS) catalyzed by TLS polymerase and error-free template switching catalyzed by RecA, and their competition on the arrested fork affects bacterial SOS mutagenesis. DnaE2 is an error-prone TLS polymerase, and its functions require ImuA and ImuB. Here we investigated the function of imuA, imuB and dnaE2 in Myxococcus xanthus and found that imuA showed differences from imuB and dnaE2 in bacterial growth, resistance and mutation frequency. Transcriptomics analysis found that ImuA were associated with bacterial SOS response. Yeast-two-hybrid scanning revealed that ImuA interacted with RecA1 besides ImuB. Protein activity analysis proved that ImuA had no DNA binding activity, but inhibited the DNA binding and recombinase activity of RecA1. These findings highlight that ImuA not only participates in TLS by binding ImuB, but also inhibits the recombinase activity of RecA1 in M. xanthus, suggesting a role of ImuA in the two replication restart pathways.ImportanceDnaE2 is responsible for bacterial SOS mutagenesis in nearly one third of sequenced bacterial strains. However, its mechanism, especially the function of its accessory protein ImuA, is still unclear. Here we reported that M. xanthus ImuA might facilitate DnaE2 TLS by inhibiting the recombinase activity of RecA1, which helps to explain the mechanism of DnaE2-dependent TLS and the scientific problem of choosing one of the two restart pathways to repair the stalled replication fork.

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Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus

Cited by 20 publications

References 41 publications

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus

Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus

ImuB and ImuC contribute to UV‐induced mutagenesis as part of the SOS regulon in Pseudomonas aeruginosa

ImuA participates in SOS mutagenesis by interacting with RecA1 and ImuB inMyxococcus xanthus

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