A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens.
Identifieur interne : 000101 ( PubMed/Corpus ); précédent : 000100; suivant : 000102A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens.
Auteurs : David R. Cameron ; Yue Shan ; Eliza A. Zalis ; Vincent Isabella ; Kim LewisSource :
- Journal of bacteriology [ 1098-5530 ] ; 2018.
English descriptors
- KwdEn :
- Adenosine Triphosphate (metabolism), Anti-Bacterial Agents (pharmacology), Biofilms (drug effects), Carbon-Nitrogen Ligases (genetics), Chloroquine (analogs & derivatives), Chloroquine (pharmacology), DNA Transposable Elements (genetics), Drug Resistance, Multiple, Bacterial (genetics), Escherichia coli (drug effects), Escherichia coli (genetics), High-Throughput Nucleotide Sequencing, Microbial Sensitivity Tests, Mutagenesis, Insertional, Pseudomonas aeruginosa (drug effects), Pseudomonas aeruginosa (genetics), Pseudomonas aeruginosa (pathogenicity).
- MESH :
- chemical , analogs & derivatives : Chloroquine.
- chemical , genetics : Carbon-Nitrogen Ligases, DNA Transposable Elements.
- chemical , metabolism : Adenosine Triphosphate.
- chemical , pharmacology : Anti-Bacterial Agents, Chloroquine.
- drug effects : Biofilms, Escherichia coli, Pseudomonas aeruginosa.
- genetics : Drug Resistance, Multiple, Bacterial, Escherichia coli, Pseudomonas aeruginosa.
- pathogenicity : Pseudomonas aeruginosa.
- High-Throughput Nucleotide Sequencing, Microbial Sensitivity Tests, Mutagenesis, Insertional.
Abstract
Persisters represent a small subpopulation of cells within a bacterial culture that are tolerant to killing by antibiotics. Persisters have been linked to recalcitrant infections caused by numerous bacterial pathogens, including Pseudomonas aeruginosa A classic example is the incurable infection of the airways for patients with cystic fibrosis. The genetic mediators of persister formation for P. aeruginosa are poorly understood. We generated a high-density transposon insertion library of P. aeruginosa PAO1 and determined the relative frequency of each insertion following fluoroquinolone treatment using transposon sequencing (Tn-seq). Of the 4,411 disrupted genes included in the screen, 137 had a ≥10-fold impact on survival. The gene disruption that resulted in the lowest survival rate was disruption of carB, which codes for the large subunit of carbamoyl phosphate synthetase (CPSase). CPSase is a metabolic enzyme that is involved in pyrimidine and arginine synthesis. Disruption of carB resulted in survival rates that were reduced by up to 2,500-fold following antibiotic treatment, and this phenotype was abolished by the addition of uracil, highlighting the importance of de novo pyrimidine biosynthesis for persister formation. Disruption of carB resulted in intracellular ATP accumulation, and lowering ATP levels using arsenate restored the antibiotic tolerance profile of the mutant to levels similar to those seen with the wild type. A decrease in ATP would lead to reduced antibiotic target activity and increased survival.IMPORTANCE Antibiotic treatment of P. aeruginosa residing in the lung of cystic fibrosis patients is ineffective. Treatment failure is attributed in part to antibiotic-tolerant phenotypic variants known as persister cells. Understanding how these cells emerge will likely inform future therapeutic strategies. In the current study, we identified carB, which codes for the large subunit of carbamoyl-phosphate synthetase, as a persister gene that contributes to multidrug tolerance in P. aeruginosa Disruption of carB resulted in a metabolic perturbation that increased cellular ATP and reduced persister formation. Conversely, lowering ATP in the mutant restored antibiotic tolerance. Our data support the hypothesis that a drop in intracellular ATP is a general mechanism of persister formation in bacteria.
DOI: 10.1128/JB.00303-18
PubMed: 29941425
Links to Exploration step
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Zalis</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Isabella, Vincent" sort="Isabella, Vincent" uniqKey="Isabella V" first="Vincent" last="Isabella">Vincent Isabella</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lewis, Kim" sort="Lewis, Kim" uniqKey="Lewis K" first="Kim" last="Lewis">Kim Lewis</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA k.lewis@northeastern.edu.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:29941425</idno><idno type="pmid">29941425</idno><idno type="doi">10.1128/JB.00303-18</idno><idno type="wicri:Area/PubMed/Corpus">000101</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000101</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens.</title><author><name sortKey="Cameron, David R" sort="Cameron, David R" uniqKey="Cameron D" first="David R" last="Cameron">David R. Cameron</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shan, Yue" sort="Shan, Yue" uniqKey="Shan Y" first="Yue" last="Shan">Yue Shan</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Zalis, Eliza A" sort="Zalis, Eliza A" uniqKey="Zalis E" first="Eliza A" last="Zalis">Eliza A. Zalis</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Isabella, Vincent" sort="Isabella, Vincent" uniqKey="Isabella V" first="Vincent" last="Isabella">Vincent Isabella</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lewis, Kim" sort="Lewis, Kim" uniqKey="Lewis K" first="Kim" last="Lewis">Kim Lewis</name><affiliation><nlm:affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA k.lewis@northeastern.edu.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Journal of bacteriology</title><idno type="eISSN">1098-5530</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Triphosphate (metabolism)</term><term>Anti-Bacterial Agents (pharmacology)</term><term>Biofilms (drug effects)</term><term>Carbon-Nitrogen Ligases (genetics)</term><term>Chloroquine (analogs & derivatives)</term><term>Chloroquine (pharmacology)</term><term>DNA Transposable Elements (genetics)</term><term>Drug Resistance, Multiple, Bacterial (genetics)</term><term>Escherichia coli (drug effects)</term><term>Escherichia coli (genetics)</term><term>High-Throughput Nucleotide Sequencing</term><term>Microbial Sensitivity Tests</term><term>Mutagenesis, Insertional</term><term>Pseudomonas aeruginosa (drug effects)</term><term>Pseudomonas aeruginosa (genetics)</term><term>Pseudomonas aeruginosa (pathogenicity)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Chloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Carbon-Nitrogen Ligases</term><term>DNA Transposable Elements</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine Triphosphate</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Chloroquine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Biofilms</term><term>Escherichia coli</term><term>Pseudomonas aeruginosa</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Drug Resistance, Multiple, Bacterial</term><term>Escherichia coli</term><term>Pseudomonas aeruginosa</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Pseudomonas aeruginosa</term></keywords><keywords scheme="MESH" xml:lang="en"><term>High-Throughput Nucleotide Sequencing</term><term>Microbial Sensitivity Tests</term><term>Mutagenesis, Insertional</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Persisters represent a small subpopulation of cells within a bacterial culture that are tolerant to killing by antibiotics. Persisters have been linked to recalcitrant infections caused by numerous bacterial pathogens, including <i>Pseudomonas aeruginosa</i> A classic example is the incurable infection of the airways for patients with cystic fibrosis. The genetic mediators of persister formation for <i>P. aeruginosa</i> are poorly understood. We generated a high-density transposon insertion library of <i>P. aeruginosa</i> PAO1 and determined the relative frequency of each insertion following fluoroquinolone treatment using transposon sequencing (Tn-seq). Of the 4,411 disrupted genes included in the screen, 137 had a ≥10-fold impact on survival. The gene disruption that resulted in the lowest survival rate was disruption of <i>carB</i>, which codes for the large subunit of carbamoyl phosphate synthetase (CPSase). CPSase is a metabolic enzyme that is involved in pyrimidine and arginine synthesis. Disruption of <i>carB</i> resulted in survival rates that were reduced by up to 2,500-fold following antibiotic treatment, and this phenotype was abolished by the addition of uracil, highlighting the importance of <i>de novo</i> pyrimidine biosynthesis for persister formation. Disruption of <i>carB</i> resulted in intracellular ATP accumulation, and lowering ATP levels using arsenate restored the antibiotic tolerance profile of the mutant to levels similar to those seen with the wild type. A decrease in ATP would lead to reduced antibiotic target activity and increased survival.<b>IMPORTANCE</b> Antibiotic treatment of <i>P. aeruginosa</i> residing in the lung of cystic fibrosis patients is ineffective. Treatment failure is attributed in part to antibiotic-tolerant phenotypic variants known as persister cells. Understanding how these cells emerge will likely inform future therapeutic strategies. In the current study, we identified <i>carB</i>, which codes for the large subunit of carbamoyl-phosphate synthetase, as a persister gene that contributes to multidrug tolerance in <i>P. aeruginosa</i> Disruption of <i>carB</i> resulted in a metabolic perturbation that increased cellular ATP and reduced persister formation. Conversely, lowering ATP in the mutant restored antibiotic tolerance. Our data support the hypothesis that a drop in intracellular ATP is a general mechanism of persister formation in bacteria.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29941425</PMID><DateCompleted><Year>2019</Year><Month>09</Month><Day>17</Day></DateCompleted><DateRevised><Year>2019</Year><Month>09</Month><Day>17</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5530</ISSN><JournalIssue CitedMedium="Internet"><Volume>200</Volume><Issue>17</Issue><PubDate><Year>2018</Year><Month>09</Month><Day>01</Day></PubDate></JournalIssue><Title>Journal of bacteriology</Title><ISOAbbreviation>J. Bacteriol.</ISOAbbreviation></Journal><ArticleTitle>A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e00303-18</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/JB.00303-18</ELocationID><Abstract><AbstractText>Persisters represent a small subpopulation of cells within a bacterial culture that are tolerant to killing by antibiotics. Persisters have been linked to recalcitrant infections caused by numerous bacterial pathogens, including <i>Pseudomonas aeruginosa</i> A classic example is the incurable infection of the airways for patients with cystic fibrosis. The genetic mediators of persister formation for <i>P. aeruginosa</i> are poorly understood. We generated a high-density transposon insertion library of <i>P. aeruginosa</i> PAO1 and determined the relative frequency of each insertion following fluoroquinolone treatment using transposon sequencing (Tn-seq). Of the 4,411 disrupted genes included in the screen, 137 had a ≥10-fold impact on survival. The gene disruption that resulted in the lowest survival rate was disruption of <i>carB</i>, which codes for the large subunit of carbamoyl phosphate synthetase (CPSase). CPSase is a metabolic enzyme that is involved in pyrimidine and arginine synthesis. Disruption of <i>carB</i> resulted in survival rates that were reduced by up to 2,500-fold following antibiotic treatment, and this phenotype was abolished by the addition of uracil, highlighting the importance of <i>de novo</i> pyrimidine biosynthesis for persister formation. Disruption of <i>carB</i> resulted in intracellular ATP accumulation, and lowering ATP levels using arsenate restored the antibiotic tolerance profile of the mutant to levels similar to those seen with the wild type. A decrease in ATP would lead to reduced antibiotic target activity and increased survival.<b>IMPORTANCE</b> Antibiotic treatment of <i>P. aeruginosa</i> residing in the lung of cystic fibrosis patients is ineffective. Treatment failure is attributed in part to antibiotic-tolerant phenotypic variants known as persister cells. Understanding how these cells emerge will likely inform future therapeutic strategies. In the current study, we identified <i>carB</i>, which codes for the large subunit of carbamoyl-phosphate synthetase, as a persister gene that contributes to multidrug tolerance in <i>P. aeruginosa</i> Disruption of <i>carB</i> resulted in a metabolic perturbation that increased cellular ATP and reduced persister formation. Conversely, lowering ATP in the mutant restored antibiotic tolerance. Our data support the hypothesis that a drop in intracellular ATP is a general mechanism of persister formation in bacteria.</AbstractText><CopyrightInformation>Copyright © 2018 American Society for Microbiology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cameron</LastName><ForeName>David R</ForeName><Initials>DR</Initials><AffiliationInfo><Affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shan</LastName><ForeName>Yue</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zalis</LastName><ForeName>Eliza A</ForeName><Initials>EA</Initials><AffiliationInfo><Affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Isabella</LastName><ForeName>Vincent</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewis</LastName><ForeName>Kim</ForeName><Initials>K</Initials><Identifier Source="ORCID">0000-0002-1335-9982</Identifier><AffiliationInfo><Affiliation>Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA k.lewis@northeastern.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>08</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Bacteriol</MedlineTA><NlmUniqueID>2985120R</NlmUniqueID><ISSNLinking>0021-9193</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004251">DNA Transposable Elements</NameOfSubstance></Chemical><Chemical><RegistryNumber>442-96-6</RegistryNumber><NameOfSubstance UI="C029563">fluoroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>886U3H6UFF</RegistryNumber><NameOfSubstance UI="D002738">Chloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>8L70Q75FXE</RegistryNumber><NameOfSubstance UI="D000255">Adenosine Triphosphate</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 6.3.-</RegistryNumber><NameOfSubstance UI="D019731">Carbon-Nitrogen Ligases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000255" MajorTopicYN="N">Adenosine Triphosphate</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018441" MajorTopicYN="N">Biofilms</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019731" MajorTopicYN="N">Carbon-Nitrogen Ligases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002738" MajorTopicYN="N">Chloroquine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004251" MajorTopicYN="N">DNA Transposable Elements</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D024901" MajorTopicYN="N">Drug Resistance, Multiple, Bacterial</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004926" MajorTopicYN="N">Escherichia coli</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D059014" MajorTopicYN="N">High-Throughput Nucleotide Sequencing</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008826" MajorTopicYN="N">Microbial Sensitivity Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016254" MajorTopicYN="N">Mutagenesis, Insertional</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011550" MajorTopicYN="N">Pseudomonas aeruginosa</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Tn-seq</Keyword><Keyword MajorTopicYN="Y">antibiotic tolerance</Keyword><Keyword MajorTopicYN="Y">persisters</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>05</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>06</Month><Day>19</Day></PubMedPubDate><PubMedPubDate 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IdType="pubmed">16768798</ArticleId></ArticleIdList></Reference><Reference><Citation>Drug Resist Updat. 2000 Aug;3(4):247-255</Citation><ArticleIdList><ArticleId IdType="pubmed">11498392</ArticleId></ArticleIdList></Reference><Reference><Citation>Microbiol Rev. 1987 Sep;51(3):341-50</Citation><ArticleIdList><ArticleId IdType="pubmed">3312985</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2015 Apr 07;6(2):null</Citation><ArticleIdList><ArticleId IdType="pubmed">25852159</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS Biol. 2010 Feb 23;8(2):e1000317</Citation><ArticleIdList><ArticleId IdType="pubmed">20186264</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2008 Aug;52(8):2718-26</Citation><ArticleIdList><ArticleId IdType="pubmed">18519731</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2013 Nov 21;503(7476):365-70</Citation><ArticleIdList><ArticleId IdType="pubmed">24226776</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2000 Sep;44(9):2242-6</Citation><ArticleIdList><ArticleId IdType="pubmed">10952562</ArticleId></ArticleIdList></Reference><Reference><Citation>Gene. 1986;48(1):119-31</Citation><ArticleIdList><ArticleId IdType="pubmed">3549457</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Microbiol. 2016 Apr 18;1:16051</Citation><ArticleIdList><ArticleId IdType="pubmed">27572649</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2017 Feb 7;8(1):</Citation><ArticleIdList><ArticleId IdType="pubmed">28174313</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2011 Jan 18;2(1):e00315-10</Citation><ArticleIdList><ArticleId IdType="pubmed">21253457</ArticleId></ArticleIdList></Reference><Reference><Citation>J Gen Microbiol. 1986 May;132(5):1297-304</Citation><ArticleIdList><ArticleId IdType="pubmed">3534137</ArticleId></ArticleIdList></Reference><Reference><Citation>Sci Rep. 2016 Feb 03;6:20519</Citation><ArticleIdList><ArticleId IdType="pubmed">26837570</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2017 Nov 22;61(12):</Citation><ArticleIdList><ArticleId IdType="pubmed">28923873</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Microbiol. 2012 Dec;10(12):841-51</Citation><ArticleIdList><ArticleId IdType="pubmed">23147702</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2017 Dec 12;8(6):</Citation><ArticleIdList><ArticleId IdType="pubmed">29233898</ArticleId></ArticleIdList></Reference><Reference><Citation>Microbiol Rev. 1987 Dec;51(4):439-57</Citation><ArticleIdList><ArticleId IdType="pubmed">3325794</ArticleId></ArticleIdList></Reference><Reference><Citation>Clin Microbiol Rev. 2007 Jul;20(3):391-408, table of contents</Citation><ArticleIdList><ArticleId IdType="pubmed">17630331</ArticleId></ArticleIdList></Reference><Reference><Citation>J Bacteriol. 2010 Dec;192(23):6191-9</Citation><ArticleIdList><ArticleId IdType="pubmed">20935098</ArticleId></ArticleIdList></Reference><Reference><Citation>Nature. 2015 Aug 6;524(7563):59-64</Citation><ArticleIdList><ArticleId IdType="pubmed">26222023</ArticleId></ArticleIdList></Reference><Reference><Citation>J Bacteriol. 2006 Jun;188(11):3826-36</Citation><ArticleIdList><ArticleId IdType="pubmed">16707675</ArticleId></ArticleIdList></Reference><Reference><Citation>Mol Syst Biol. 2006;2:2006.0008</Citation><ArticleIdList><ArticleId IdType="pubmed">16738554</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14339-44</Citation><ArticleIdList><ArticleId IdType="pubmed">14617778</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Respir Crit Care Med. 2003 Oct 15;168(8):918-51</Citation><ArticleIdList><ArticleId IdType="pubmed">14555458</ArticleId></ArticleIdList></Reference><Reference><Citation>J Bacteriol. 2006 Jul;188(14):5136-44</Citation><ArticleIdList><ArticleId IdType="pubmed">16816185</ArticleId></ArticleIdList></Reference><Reference><Citation>Mol Cell. 2013 Oct 24;52(2):248-54</Citation><ArticleIdList><ArticleId IdType="pubmed">24095282</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Rev Microbiol. 2007 Jan;5(1):48-56</Citation><ArticleIdList><ArticleId IdType="pubmed">17143318</ArticleId></ArticleIdList></Reference><Reference><Citation>FEMS Microbiol Lett. 2004 Sep 1;238(1):23-8</Citation><ArticleIdList><ArticleId IdType="pubmed">15336398</ArticleId></ArticleIdList></Reference><Reference><Citation>Annu Rev Microbiol. 2010;64:357-72</Citation><ArticleIdList><ArticleId IdType="pubmed">20528688</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Chem Biol. 2017 Feb 16;24(2):195-206</Citation><ArticleIdList><ArticleId IdType="pubmed">28111098</ArticleId></ArticleIdList></Reference><Reference><Citation>N Engl J Med. 1999 Jan 7;340(1):23-30</Citation><ArticleIdList><ArticleId IdType="pubmed">9878641</ArticleId></ArticleIdList></Reference><Reference><Citation>J Bacteriol. 1983 Aug;155(2):768-75</Citation><ArticleIdList><ArticleId IdType="pubmed">6348026</ArticleId></ArticleIdList></Reference><Reference><Citation>Microbiology. 2012 Dec;158(Pt 12):3014-9</Citation><ArticleIdList><ArticleId IdType="pubmed">23023972</ArticleId></ArticleIdList></Reference><Reference><Citation>J Bacteriol. 2008 Dec;190(24):7910-7</Citation><ArticleIdList><ArticleId IdType="pubmed">18849421</ArticleId></ArticleIdList></Reference><Reference><Citation>Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):4110-5</Citation><ArticleIdList><ArticleId IdType="pubmed">25775563</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Methods. 2006 Aug;3(8):623-8</Citation><ArticleIdList><ArticleId IdType="pubmed">16862137</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochim Biophys Acta. 1967;145(3):843-4</Citation><ArticleIdList><ArticleId IdType="pubmed">4863911</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2014 Dec 4;159(6):1300-11</Citation><ArticleIdList><ArticleId IdType="pubmed">25480295</ArticleId></ArticleIdList></Reference><Reference><Citation>Front Microbiol. 2017 Oct 04;8:1917</Citation><ArticleIdList><ArticleId IdType="pubmed">29046671</ArticleId></ArticleIdList></Reference><Reference><Citation>Nat Methods. 2009 Oct;6(10):767-72</Citation><ArticleIdList><ArticleId IdType="pubmed">19767758</ArticleId></ArticleIdList></Reference><Reference><Citation>Nucleic Acids Res. 2016 Jan 4;44(D1):D646-53</Citation><ArticleIdList><ArticleId IdType="pubmed">26578582</ArticleId></ArticleIdList></Reference><Reference><Citation>J Med Microbiol. 2016 Aug;65(8):848-57</Citation><ArticleIdList><ArticleId IdType="pubmed">27375177</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 2005 Apr;49(4):1483-94</Citation><ArticleIdList><ArticleId IdType="pubmed">15793130</ArticleId></ArticleIdList></Reference><Reference><Citation>MBio. 2013 Feb 12;4(1):e00537-12</Citation><ArticleIdList><ArticleId IdType="pubmed">23404398</ArticleId></ArticleIdList></Reference><Reference><Citation>Antimicrob Agents Chemother. 1996 Sep;40(9):2021-8</Citation><ArticleIdList><ArticleId IdType="pubmed">8878574</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= A Genetic Determinant of Persister Cell Formation in Bacterial Pathogens.
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