FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3165669060> ?p ?o ?g. }

• W3165669060 endingPage "R495" @default.
• W3165669060 startingPage "R493" @default.
• W3165669060 abstract "In a new paper in this issue, Murawski and Brynildsen define chromosomal ploidy as an important characteristic for persistence following fluoroquinolone treatment. Bacteria carrying two chromosomes are more likely to repair DNA damage through homologous recombination compared with cells containing a single chromosome. In a new paper in this issue, Murawski and Brynildsen define chromosomal ploidy as an important characteristic for persistence following fluoroquinolone treatment. Bacteria carrying two chromosomes are more likely to repair DNA damage through homologous recombination compared with cells containing a single chromosome. All bacterial populations contain a small fraction of transiently antibiotic-tolerant ‘persister’ cells. Persisters are phenotypic variants that survive antibiotic treatment and can form a new bacterial population upon antibiotic removal (Figure 1)1Wilmaerts D. Windels E.M. Verstraeten N. Michiels J. General mechanisms leading to persister formation and awakening.Trends Genet. 2019; 35: 401-411Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar,2Balaban N.Q. Helaine S. Lewis K. Ackermann M. Aldridge B. Andersson D.I. Brynildsen M.P. Bumann D. Camilli A. Collins J.J. et al.Definitions and guidelines for research on antibiotic persistence.Nat. Rev. Microbiol. 2019; 17: 441-448Crossref PubMed Scopus (364) Google Scholar. Importantly, this new population does not maintain the antibiotic-tolerant phenotype of the founding persister cell. Instead, its progeny are antibiotic sensitive again, yet eventually a small fraction of new persister cells is established. Although persisters arise spontaneously in a population, the majority of the persister cells are induced in response to different stresses, such as nutrient deprivation1Wilmaerts D. Windels E.M. Verstraeten N. Michiels J. General mechanisms leading to persister formation and awakening.Trends Genet. 2019; 35: 401-411Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar,3Balaban N.Q. Merrin J. Chait R. Kowalik L. Leibler S. Bacterial persistence as a phenotypic switch.Science. 2004; 305: 1622-1625Crossref PubMed Scopus (1911) Google Scholar. Persisters pose a threat to public health, as they are held responsible for the recalcitrance of several chronic infections4Mulcahy L.R. Burns J.L. Lory S. Lewis K. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis.J. Bacteriol. 2010; 192: 6191-6199Crossref PubMed Scopus (390) Google Scholar, and they form a pool from which resistant mutants can emerge5Windels E.M. Michiels J.E. Fauvart M. Wenseleers T. Van den Bergh B. Michiels J. Bacterial persistence promotes the evolution of antibiotic resistance by increasing survival and mutation rates.ISME J. 2019; 13: 1239-1251Crossref PubMed Scopus (119) Google Scholar,6Levin-Reisman I. Ronin I. Gefen O. Braniss I. Shoresh N. Balaban N.Q. Antibiotic tolerance facilitates the evolution of resistance.Science. 2017; 355: 826-830Crossref PubMed Scopus (514) Google Scholar. The fraction of persister cells in a given bacterial population varies depending on the antibiotic used, demonstrating that different molecular mechanisms induce persistence. In recent years, several general models have been proposed to explain the molecular state of the persister phenotype. For a long time, persisters were thought to be non-growing, dormant cells. In addition, the hypothesis of an inactive antibiotic target was postulated7Lewis K. Persister cells.Annu. Rev. Microbiol. 2010; 64: 357-372Crossref PubMed Scopus (1295) Google Scholar. Although these molecular states hold true for a fraction of the persister population, they are clearly not inclusive. Indeed, recent work has demonstrated the presence of active persister mechanisms, antibiotic-inflicted damage, and persister cells displaying slow growth1Wilmaerts D. Windels E.M. Verstraeten N. Michiels J. General mechanisms leading to persister formation and awakening.Trends Genet. 2019; 35: 401-411Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar,8Goormaghtigh F. Van Melderen L. Single-cell imaging and characterization of Escherichia coli persister cells to ofloxacin in exponential cultures.Sci. Adv. 2019; 5eaav9462Crossref PubMed Scopus (60) Google Scholar,9Völzing K.G. Brynildsen M.P. Stationary-phase persisters to ofloxacin sustain DNA damage and require repair systems only during recovery.mBio. 2015; 6 (e00731–15)Crossref PubMed Scopus (72) Google Scholar. A new study by Murawski and Brynildsen, published in this issue of Current Biology, sheds light on ploidy as an important phenotypic variable in fluoroquinolone persistence and reveals persister heterogeneity at the single-cell level10Murawski A.M. Brynildsen M.P. Ploidy is an important determinant of fluoroquinolone persister survival.Curr. Biol. 2021; 31: 2039-2050Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar. Bacteria are generally assumed to be monoploid, having only a single copy of the chromosome. However, in reality, depending on their growth status, bacteria might contain several copies of the chromosome; for example when re-initiation of replication occurs before cell division takes place11Pecoraro V. Zerulla K. Lange C. Soppa J. Quantification of ploidy in proteobacteria revealed the existence of monoploid, (mero-)oligoploid and polyploid species.PLoS One. 2011; 6e16392Crossref PubMed Scopus (68) Google Scholar,12Akerlund T. Nordstrom K. Bernander R. Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli.J. Bacteriol. 1995; 177: 6791-6797Crossref PubMed Google Scholar. Fluoroquinolones are antibiotics that target DNA gyrase and topoisomerase IV, causing the formation of double-stranded DNA breaks and eventually leading to bacterial cell death if these breaks are not repaired. Repair of double-stranded breaks commonly occurs via RecA-mediated homologous recombination13Sinha A.K. Possoz C. Leach D.R.F. The roles of bacterial DNA double-strand break repair proteins in chromosomal DNA replication.FEMS Microbiol. Rev. 2020; 44: 351-368Crossref PubMed Scopus (13) Google Scholar. The Brynildsen group has previously demonstrated that persister cells acquire DNA damage upon treatment with fluoroquinolones and that this damage is repaired during recovery9Völzing K.G. Brynildsen M.P. Stationary-phase persisters to ofloxacin sustain DNA damage and require repair systems only during recovery.mBio. 2015; 6 (e00731–15)Crossref PubMed Scopus (72) Google Scholar. These findings contradicted the general assumption that persisters survive antibiotic treatment due to target inactivity. Later, they showed that persisters have a delayed growth resumption compared to antibiotic-sensitive cells upon transferring the cells to an environment containing fresh nutrients. This delay enables a persister cell to repair the DNA damage before growth initiation takes place. Strikingly, nearly 100% survival following fluoroquinolone treatment is observed if growth resumption is delayed at the population level14Mok W.W.K. Brynildsen M.P. Timing of DNA damage responses impacts persistence to fluoroquinolones.Proc. Natl. Acad. Sci. USA. 2018; 115: e6301-e6309Crossref PubMed Scopus (52) Google Scholar. In the current study, the authors expand the model of fluoroquinolone persisters and show that damage repair is affected by the number of chromosome copies in the bacterial cell. By fluorescently visualizing the bacterial chromosome, either via DNA staining or by using a parS–ParB origin–reporter strain, the number of chromosomes was enumerated for every bacterial cell. Fluorescence-activated single-cell sorting was employed to sort cells based on DNA content, demonstrating that the subpopulation with two chromosomes contained up to 16 times as many persisters compared to the subpopulation with one chromosome upon treatment with fluoroquinolones. This increased survival in the two-chromosome population results from the ability to repair the antibiotic-inflicted double-stranded DNA breaks through homologous recombination by using the second copy of the genome as a template10Murawski A.M. Brynildsen M.P. Ploidy is an important determinant of fluoroquinolone persister survival.Curr. Biol. 2021; 31: 2039-2050Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar. Next, the authors turned their attention to the one-chromosome subpopulation. These cells do not have a second genomic copy and have therefore a compromised capability to perform homologous recombination. Intriguingly, persisters arose from this population at a 10-fold higher frequency compared to homologous-recombination-deficient ΔrecA and ΔrecB mutants, pointing towards a different repair mechanism that is independent of an additional copy of the genome but might be dependent on recombination between repetitive sequences. The type of damage and the molecular mechanisms underlying the repair are interesting topics for further work. Using time-lapse microscopy, one- and two-chromosome persisters were tracked during recovery after antibiotic treatment. Interestingly, differences in growth dynamics were observed between the two persister populations. These dynamics were specific for persister cells, as no significant difference between the two subpopulations was detected in an untreated population. Both subpopulations were found to elongate strongly before cell division takes place, but the rate of expansion was slower in the one-chromosome-persister population compared to the two-chromosome-persister population. In addition, the time of cell division was later in one-chromosome persisters compared to two-chromosome persisters. A strong elongation of fluoroquinolone-treated cells was observed previously8Goormaghtigh F. Van Melderen L. Single-cell imaging and characterization of Escherichia coli persister cells to ofloxacin in exponential cultures.Sci. Adv. 2019; 5eaav9462Crossref PubMed Scopus (60) Google Scholar and was partly attributed to the induction of the SOS response, which inhibits cell division, but not elongation, until the DNA damage is repaired. In line with this view, the authors demonstrated that both one- and two-chromosome persister cells suffer DNA damage upon treatment with fluoroquinolones, although there might be differences in the extent of the damage that goes undetected. As the ParB foci are perturbed as soon as a single double-stranded break occurs15Badrinarayanan A. Le T.B.K. Laub M.T. Rapid pairing and resegregation of distant homologous loci enables double-strand break repair in bacteria.J. Cell Biol. 2015; 210: 385-400Crossref PubMed Scopus (30) Google Scholar, a quantitative analysis of the DNA damage in both subpopulations of persister cells was not possible. An interesting possibility would be that the repair orchestrated in one-chromosome persisters is slower, resulting in the slower rate of expansion. To date, little is known about the heterogeneity of persisters. In the seminal paper from Balaban et al., both non-growing persisters, generated at stationary phase, and spontaneously formed slow-growing persisters were described to be present in a persister population3Balaban N.Q. Merrin J. Chait R. Kowalik L. Leibler S. Bacterial persistence as a phenotypic switch.Science. 2004; 305: 1622-1625Crossref PubMed Scopus (1911) Google Scholar. In addition, nutrient shifts were shown to form ampicillin-tolerant and ofloxacin-tolerant persister cells via different molecular pathways16Amato S.M. Brynildsen M.P. Persister heterogeneity arising from a single metabolic stress.Curr. Biol. 2015; 25: 2090-2098Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar. However, it is unknown whether these different populations have different regrowth kinetics upon nutrient replenishment. In this paper, Murawski and Brynildsen experimentally verifed the presence of two distinct persister subpopulations containing one or two chromosome copies. Furthermore, they demonstrated that these subpopulations have different regrowth kinetics and molecular mechanisms underlying antibiotic survival, underscoring the importance of investigating persister recovery at the single-cell level. This paper demonstrates the importance of antibiotic-inflicted repair processes in persister cells and, more specifically, after fluoroquinolone treatment. However, several questions remain. How do persister cells delay growth resumption until DNA damage is repaired? Do other types of antibiotics, such as aminoglycosides and β-lactams, also inflict other types of damage to the persister cell that need repair for successful persister awakening? Indeed, previous work has demonstrated aberrant outgrowth phenotypes after ceftazidime treatment17Wilmaerts D. Dewachter L. De Loose P.-J. Bollen C. Verstraeten N. Michiels J. HokB monomerization and membrane repolarization control persister awakening.Mol. Cell. 2019; 75: 1031-1042Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, suggesting that repair is inherently linked with the persister phenotype. Furthermore, how is the DNA damage repaired in one-chromosome persisters and why is the majority of two-chromosome cells not capable of repairing DNA damage, despite having a second copy? Continued efforts are needed to understand the persister phenotype in more detail, preferentially at the single-cell level. This paper sheds light onto a hitherto-unknown facet of the persister phenotype and urges the field to step away from the idea that persistence is solely based on passive mechanisms." @default.
• W3165669060 created "2021-06-07" @default.
• W3165669060 creator A5019196159 @default.
• W3165669060 creator A5063661741 @default.
• W3165669060 date "2021-05-01" @default.
• W3165669060 modified "2023-09-27" @default.
• W3165669060 title "Antibiotic persistence: The power of being a diploid" @default.
• W3165669060 cites W1934154653 @default.
• W3165669060 cites W2013737863 @default.
• W3165669060 cites W2107600014 @default.
• W3165669060 cites W2109523604 @default.
• W3165669060 cites W2131135346 @default.
• W3165669060 cites W2141883227 @default.
• W3165669060 cites W2148323109 @default.
• W3165669060 cites W2586590237 @default.
• W3165669060 cites W2809128197 @default.
• W3165669060 cites W2910584283 @default.
• W3165669060 cites W2940117744 @default.
• W3165669060 cites W2941980995 @default.
• W3165669060 cites W2950588209 @default.
• W3165669060 cites W2961575477 @default.
• W3165669060 cites W3016167589 @default.
• W3165669060 cites W3135323878 @default.
• W3165669060 cites W4213353716 @default.
• W3165669060 doi "https://doi.org/10.1016/j.cub.2021.03.072" @default.
• W3165669060 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34033776" @default.
• W3165669060 hasPublicationYear "2021" @default.
• W3165669060 type Work @default.
• W3165669060 sameAs 3165669060 @default.
• W3165669060 citedByCount "1" @default.
• W3165669060 countsByYear W31656690602022 @default.
• W3165669060 crossrefType "journal-article" @default.
• W3165669060 hasAuthorship W3165669060A5019196159 @default.
• W3165669060 hasAuthorship W3165669060A5063661741 @default.
• W3165669060 hasBestOaLocation W31656690601 @default.
• W3165669060 hasConcept C104317684 @default.
• W3165669060 hasConcept C127413603 @default.
• W3165669060 hasConcept C143191323 @default.
• W3165669060 hasConcept C187320778 @default.
• W3165669060 hasConcept C2781009140 @default.
• W3165669060 hasConcept C54355233 @default.
• W3165669060 hasConcept C78458016 @default.
• W3165669060 hasConcept C86803240 @default.
• W3165669060 hasConceptScore W3165669060C104317684 @default.
• W3165669060 hasConceptScore W3165669060C127413603 @default.
• W3165669060 hasConceptScore W3165669060C143191323 @default.
• W3165669060 hasConceptScore W3165669060C187320778 @default.
• W3165669060 hasConceptScore W3165669060C2781009140 @default.
• W3165669060 hasConceptScore W3165669060C54355233 @default.
• W3165669060 hasConceptScore W3165669060C78458016 @default.
• W3165669060 hasConceptScore W3165669060C86803240 @default.
• W3165669060 hasFunder F4320321730 @default.
• W3165669060 hasFunder F4320322308 @default.
• W3165669060 hasIssue "10" @default.
• W3165669060 hasLocation W31656690601 @default.
• W3165669060 hasOpenAccess W3165669060 @default.
• W3165669060 hasPrimaryLocation W31656690601 @default.
• W3165669060 hasRelatedWork W1578739828 @default.
• W3165669060 hasRelatedWork W1593206460 @default.
• W3165669060 hasRelatedWork W1899420018 @default.
• W3165669060 hasRelatedWork W2002221633 @default.
• W3165669060 hasRelatedWork W2014964654 @default.
• W3165669060 hasRelatedWork W2318043644 @default.
• W3165669060 hasRelatedWork W2327471993 @default.
• W3165669060 hasRelatedWork W2980025597 @default.
• W3165669060 hasRelatedWork W4238365180 @default.
• W3165669060 hasRelatedWork W4256630193 @default.
• W3165669060 hasVolume "31" @default.
• W3165669060 isParatext "false" @default.
• W3165669060 isRetracted "false" @default.
• W3165669060 magId "3165669060" @default.
• W3165669060 workType "article" @default.