{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:43:19Z","timestamp":1777588999879,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T00:00:00Z","timestamp":1557187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 &gt; 5000 \u00b5g\/mL), however, it (at 100 and 200 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/molecules24091757","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"1757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Betulinic Acid Prevents the Acquisition of Ciprofloxacin-Mediated Mutagenesis in Staphylococcus aureus"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-3036","authenticated-orcid":false,"given":"Alexsander Rodrigues","family":"Carvalho Junior","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur Lima de Berredo","family":"Martins","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda da Silva","family":"Cutrim","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deivid Martins","family":"Santos","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermerson Sousa","family":"Maia","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari Silma Maia da","family":"Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrielle","family":"Zagmignan","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8685-7608","authenticated-orcid":false,"given":"Maria Raimunda Chagas","family":"Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina de Andrade","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle Maria Skelding Pinheiro","family":"Guilhon","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Exatas e Naturais, Universidade Federal do Par\u00e1, B\u00e9lem 66075-110, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2009-2817","authenticated-orcid":false,"given":"Ant\u00f4nio Jos\u00e9","family":"Cantanhede Filho","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Instituto Federal do Maranh\u00e3o, S\u00e3o Lu\u00eds, Maranh\u00e3o 65030-005, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4206-0904","authenticated-orcid":false,"given":"Lu\u00eds Cl\u00e1udio","family":"Nascimento da Silva","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o, Universidade Ceuma, S\u00e3o Lu\u00eds, Maranh\u00e3o 65075-120, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,7]]},"reference":[{"key":"ref_1","first-page":"23","article-title":"Changes in bacterial hospital epidemiology","volume":"31","author":"Morosini","year":"2018","journal-title":"Rev. Esp. De Quimioter. Publ. Of. De La Soc. Esp. De Quimioter."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Monserrat-Martinez, A., Gambin, Y., and Sierecki, E. (2019). Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061255"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00088-17","DOI":"10.1128\/CMR.00088-17","article-title":"Mobile Genetic Elements Associated with Antimicrobial Resistance","volume":"31","author":"Partridge","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00023-18","DOI":"10.1128\/CMR.00023-18","article-title":"Mechanisms of Bacterial Tolerance and Persistence in the Gastrointestinal and Respiratory Environments","volume":"31","author":"Trastoy","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.3389\/fmicb.2018.02102","article-title":"Antimicrobial Resistance Distribution Differs Among Methicillin Resistant Staphylococcus aureus Sequence Type (ST) 5 Isolates From Health Care and Agricultural Sources","volume":"9","author":"Hau","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_6","first-page":"2588","article-title":"Analysis of antimicrobial resistance and risk factors of community-onset methicillin-resistant staphylococcus aureus infection","volume":"98","author":"Shen","year":"2018","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.adaj.2018.05.034","article-title":"The use and misuse of antibiotics in dentistry: A scoping review","volume":"149","author":"Stein","year":"2018","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1158\/1538-7445.AM2018-2838","article-title":"Abstract 2838: Discovery of adaptive resistance pathways and anti-resistance combination therapies in cancer from phosphoproteomic data","volume":"78","author":"Luna","year":"2018","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jhin.2010.05.020","article-title":"Does microbial resistance or adaptation to biocides create a hazard in infection prevention and control?","volume":"76","author":"Meyer","year":"2010","journal-title":"J. Hosp. Infect."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/wsbm.1335","article-title":"Adaptive resistance to antibiotics in bacteria: a systems biology perspective","volume":"8","author":"Aldana","year":"2016","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.3389\/fmicb.2017.01360","article-title":"The Transient Multidrug Resistance Phenotype of Salmonella enterica Swarming Cells Is Abolished by Sub-inhibitory Concentrations of Antimicrobial Compounds","volume":"8","author":"Irazoki","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.dnarep.2017.09.003","article-title":"Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus","volume":"59","author":"Alves","year":"2017","journal-title":"DNA Repair"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1146\/annurev-micro-090817-062139","article-title":"Antibiotic-Induced Genetic Variation: How It Arises and How It Can Be Prevented","volume":"72","author":"Blazquez","year":"2018","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E6301","DOI":"10.1073\/pnas.1804218115","article-title":"Timing of DNA damage responses impacts persistence to fluoroquinolones","volume":"115","author":"Mok","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.molcel.2018.07.037","article-title":"Mycobacterial Mutagenesis and Drug Resistance Are Controlled by Phosphorylation- and Cardiolipin-Mediated Inhibition of the RecA Coprotease","volume":"72","author":"Wipperman","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Michel, B. (2005). After 30 years of study, the bacterial SOS response still surprises us. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030255"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"410","DOI":"10.3389\/fcimb.2018.00410","article-title":"Zinc Blockade of SOS Response Inhibits Horizontal Transfer of Antibiotic Resistance Genes in Enteric Bacteria","volume":"8","author":"Crane","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.3389\/fmicb.2018.01212","article-title":"DnaA and LexA Proteins Regulate Transcription of the uvrB Gene in Escherichia coli: The Role of DnaA in the Control of the SOS Regulon","volume":"9","author":"Wurihan","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Witkowski, T.A., Grice, A.N., Stinnett, D.B., Wells, W.K., Peterson, M.A., and Hare, J.M. (2016). UmuDAb: An Error-Prone Polymerase Accessory Homolog Whose N-Terminal Domain Is Required for Repression of DNA Damage Inducible Gene Expression in Acinetobacter baylyi. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152013"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1021\/acs.biochem.6b00117","article-title":"Mutations for Worse or Better: Low-Fidelity DNA Synthesis by SOS DNA Polymerase V Is a Tightly Regulated Double-Edged Sword","volume":"55","author":"Jaszczur","year":"2016","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1021\/acs.biochem.7b00560","article-title":"Identification of the Dimer Exchange Interface of the Bacterial DNA Damage Response Protein UmuD","volume":"56","author":"Murison","year":"2017","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vestergaard, M., Paulander, W., and Ingmer, H. (2015). Activation of the SOS response increases the frequency of small colony variants. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1735-2"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1128\/IAI.03016-14","article-title":"Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response","volume":"83","author":"Painter","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01439-18","DOI":"10.1128\/AAC.01439-18","article-title":"Antibiotics Stimulate Formation of Vesicles in Staphylococcus aureus in both Phage-Dependent and -Independent Fashions and via Different Routes","volume":"63","author":"Andreoni","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Meunier, A., Nerich, V., Fagnoni-Legat, C., Richard, M., Mazel, D., Adotevi, O., Bertrand, X., and Hocquet, D. (2019). Enhanced emergence of antibiotic-resistant pathogenic bacteria after in vitro induction with cancer chemotherapy drugs. J. Antimicrob. Chemother.","DOI":"10.1093\/jac\/dkz070"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e00971-17","DOI":"10.1128\/mBio.00971-17","article-title":"Quinolone Resistance Reversion by Targeting the SOS Response","volume":"8","author":"Recacha","year":"2017","journal-title":"mBio"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e02107","DOI":"10.1128\/AAC.02107-16","article-title":"Ciprofloxacin-Mediated Mutagenesis Is Suppressed by Subinhibitory Concentrations of Amikacin in Pseudomonas aeruginosa","volume":"61","author":"Valencia","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.3389\/fmicb.2018.02961","article-title":"Advancement of the 5-Amino-1-(Carbamoylmethyl)-1H-1,2,3-Triazole-4-Carboxamide Scaffold to Disarm the Bacterial SOS Response","volume":"9","author":"Selwood","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.21873\/invivo.11349","article-title":"Antitumor Activity of Betulinic Acid and Betulin in Canine Cancer Cell Lines","volume":"32","author":"Zhao","year":"2018","journal-title":"Vivo"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7065","DOI":"10.1021\/acs.jafc.8b02992","article-title":"New Insights into the Inhibition Mechanism of Betulinic Acid on alpha-Glucosidase","volume":"66","author":"Ding","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/j.pain.0000000000001385","article-title":"Betulinic acid, derived from the desert lavender Hyptis emoryi, attenuates paclitaxel-, HIV-, and nerve injury-associated peripheral sensory neuropathy via block of N- and T-type calcium channels","volume":"160","author":"Bellampalli","year":"2019","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kutkowska, J., Strzadala, L., and Rapak, A. (2018). Sorafenib in Combination with Betulinic Acid Synergistically Induces Cell Cycle Arrest and Inhibits Clonogenic Activity in Pancreatic Ductal Adenocarcinoma Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103234"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kahnt, M., Fischer Nee Heller, L., Al-Harrasi, A., and Csuk, R. (2018). Ethylenediamine Derived Carboxamides of Betulinic and Ursolic Acid as Potential Cytotoxic Agents. Molecules, 23.","DOI":"10.3390\/molecules23102558"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Sousa, J.L.C., Freire, C.S.R., Silvestre, A.J.D., and Silva, A.M.S. (2019). Recent Developments in the Functionalization of Betulinic Acid and Its Natural Analogues: A Route to New Bioactive Compounds. Molecules, 24.","DOI":"10.3390\/molecules24020355"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1515\/znc-2003-1-213","article-title":"Constituents of Antibacterial Extract of Caesalpinia paraguariensis Burk","volume":"58","year":"2003","journal-title":"Z. Naturforsch. C"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.fitote.2014.01.026","article-title":"Potential targets by pentacyclic triterpenoids from Callicarpa farinosa against methicillin-resistant and sensitive Staphylococcus aureus","volume":"94","author":"Chung","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1055\/s-0043-123472","article-title":"New Pharmacological Opportunities for Betulinic Acid","volume":"84","author":"Rios","year":"2018","journal-title":"Planta Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/nyas.13570","article-title":"Therapeutic applications of betulinic acid nanoformulations","volume":"1421","author":"Saneja","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_39","first-page":"252","article-title":"Triterpenoides, fen\u00f3licos e efeito fitot\u00f3xico das folhas de Eugenia flavescens DC (Myrtaceae)","volume":"40","author":"Santos","year":"2018","journal-title":"Qu\u00edmica Nova"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gottschalk, S., Ifrah, D., Lerche, S., Gottlieb, C.T., Cohn, M.T., Hiasa, H., Hansen, P.R., Gram, L., Ingmer, H., and Thomsen, L.E. (2013). The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus. BMC Microbiol., 13.","DOI":"10.1186\/1471-2180-13-192"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jaszczur, M.M., Vo, D.D., Stanciauskas, R., Bertram, J.G., Sikand, A., Cox, M.M., Woodgate, R., Mak, C.H., Pinaud, F., and Goodman, M.F. (2019). Conformational regulation of Escherichia coli DNA polymerase V by RecA and ATP. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1007956"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3389\/fmicb.2018.01438","article-title":"DNA Damage Repair and Drug Efflux as Potential Targets for Reversing Low or Intermediate Ciprofloxacin Resistance in E. coli K-12","volume":"9","author":"Klitgaard","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.mib.2012.07.007","article-title":"Antimicrobials as promoters of genetic variation","volume":"15","author":"Blazquez","year":"2012","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/em.22267","article-title":"The SOS System: A Complex and Tightly Regulated Response to DNA Damage","volume":"60","author":"Maslowska","year":"2019","journal-title":"Environ. Mol. Mutagenesis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1089\/fpd.2014.1824","article-title":"Effect of rifampicin and gentamicin on Shiga toxin 2 expression level and the SOS response in Escherichia coli O104:H4","volume":"12","author":"Fadlallah","year":"2015","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1126\/science.1101630","article-title":"SOS response induction by beta-lactams and bacterial defense against antibiotic lethality","volume":"305","author":"Miller","year":"2004","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, C.M., Chen, H.T., Wu, Z.Y., Jhan, Y.L., Shyu, C.L., and Chou, C.H. (2016). Antibacterial and Synergistic Activity of Pentacyclic Triterpenoids Isolated from Alstonia scholaris. Molecules, 21.","DOI":"10.3390\/molecules21020139"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jep.2008.09.001","article-title":"Ursolic, oleanolic and betulinic acids: antibacterial spectra and selectivity indexes","volume":"120","author":"Fontanay","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.micpath.2017.08.012","article-title":"Influence of oxidative stress on the antibacterial activity of betulin, betulinic acid and ursolic acid","volume":"111","author":"Oloyede","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jep.2016.04.052","article-title":"Antimycobacterial triterpenes from the Canadian medicinal plant Sarracenia purpurea","volume":"188","author":"Morrison","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e00163-16","DOI":"10.1128\/mSphere.00163-16","article-title":"Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics","volume":"1","author":"Mo","year":"2016","journal-title":"mSphere"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.chembiol.2016.02.010","article-title":"RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance","volume":"23","author":"Alam","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3109\/10409238.2010.480968","article-title":"A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V","volume":"45","author":"Patel","year":"2010","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"a012674","DOI":"10.1101\/cshperspect.a012674","article-title":"DNA damage responses in prokaryotes: regulating gene expression, modulating growth patterns, and manipulating replication forks","volume":"5","author":"Kreuzer","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e01426-14","DOI":"10.1128\/mBio.01426-14","article-title":"Apoptosis-like death, an extreme SOS response in Escherichia coli","volume":"5","author":"Erental","year":"2014","journal-title":"mBio"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Erental, A., Sharon, I., and Engelberg-Kulka, H. (2012). Two Programmed Cell Death Systems in Escherichia coli: An Apoptotic-Like Death Is Inhibited by the mazEF-Mediated Death Pathway. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001281"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1007\/s00253-018-9561-9","article-title":"Induction of apoptosis-like death by periplanetasin-2 in Escherichia coli and contribution of SOS genes","volume":"103","author":"Lee","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"18096","DOI":"10.1073\/pnas.1213332109","article-title":"BapE DNA endonuclease induces an apoptotic-like response to DNA damage in Caulobacter","volume":"109","author":"Bos","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00203-013-0906-6","article-title":"A component of gamma-radiation-induced cell death in E. coli is programmed and interlinked with activation of caspase-3 and SOS response","volume":"195","author":"Wadhawan","year":"2013","journal-title":"Arch. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/jac\/dkq496","article-title":"Effect of recA inactivation on mutagenesis of Escherichia coli exposed to sublethal concentrations of antimicrobials","volume":"66","author":"Thi","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Figueiredo, C., Branco Santos, J.C., Castro Junior, J.A.A., Wakui, V.G., Rodrigues, J.F.S., Arruda, M.O., Monteiro, A.S., Monteiro-Neto, V., Bomfim, M.R.Q., and Kato, L. (2017). Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities. Molecules, 22.","DOI":"10.3390\/molecules22060910"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.3389\/fmicb.2016.02052","article-title":"Cinnamaldehyde Inhibits Staphylococcus aureus Virulence Factors and Protects against Infection in a Galleria mellonella Model","volume":"7","author":"Ferro","year":"2016","journal-title":"Front. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/9\/1757\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:49:34Z","timestamp":1760186974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/9\/1757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,7]]},"references-count":62,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["molecules24091757"],"URL":"https:\/\/doi.org\/10.3390\/molecules24091757","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,7]]}}}