Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria
Publication Date
October 02, 2015
Journal
PLOS Genetics
Authors
Alexandro Rodríguez-Rojas, Olga Makarova, Uta Müller & Jens Rolff
Volume
11
Issue
10
Pages
e1005546
DOI
https://dx.plos.org/10.1371/journal.pgen.1005546
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1005546
Web of Science
000364401600019
Scopus
84946600759
Mendeley
http://www.mendeley.com/research/cationic-peptides-facilitate-ironinduced-mutagenesis-bacteria
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2297892"], "description"=>"<p>The interactions of LL-37 with the membrane at sub-inhibitory concentrations lead to transient permeability changes in the membranes that promote iron movement in favour of the electrochemical gradient. Uncontrolled uptake of ferrous ions stimulates Fenton reaction that leads to hydroxyl radical formation and results in DNA damage and mutagenesis.</p>", "links"=>[], "tags"=>["fibrosis patients", "Free iron concentration", "mutation rate", "Reactive oxygen species", "cationic antimicrobial peptides", "dna", "Bacteria Pseudomonas aeruginosa", "ll", "Fenton reaction fingerprints"], "article_id"=>1563550, "categories"=>["Uncategorised"], "users"=>["Alexandro Rodríguez-Rojas", "Olga Makarova", "Uta Müller", "Jens Rolff"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005546.g005", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_model_for_LL_37_mediated_iron_induced_mutagenesis_in_Pseudomonas_aeruginosa_/1563550", "title"=>"A model for LL-37-mediated, iron–induced mutagenesis in <i>Pseudomonas aeruginosa</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 04:10:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297889"], "description"=>"<p>The mutation rate is only increased if both, iron and colistin, are present. Error bars represent 95% confidence intervals for mutation rates.</p>", "links"=>[], "tags"=>["fibrosis patients", "Free iron concentration", "mutation rate", "Reactive oxygen species", "cationic antimicrobial peptides", "dna", "Bacteria Pseudomonas aeruginosa", "ll", "Fenton reaction fingerprints"], "article_id"=>1563547, "categories"=>["Uncategorised"], "users"=>["Alexandro Rodríguez-Rojas", "Olga Makarova", "Uta Müller", "Jens Rolff"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005546.g003", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutagenesis_induced_by_colistin_and_Fe_2_combination_/1563547", "title"=>"Mutagenesis induced by colistin and Fe<sup>2+</sup> combination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 04:10:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297908", "https://ndownloader.figshare.com/files/2297909", "https://ndownloader.figshare.com/files/2297910", "https://ndownloader.figshare.com/files/2297911", "https://ndownloader.figshare.com/files/2297912", "https://ndownloader.figshare.com/files/2297913", "https://ndownloader.figshare.com/files/2297914", "https://ndownloader.figshare.com/files/2297915", "https://ndownloader.figshare.com/files/2297916", "https://ndownloader.figshare.com/files/2297917", "https://ndownloader.figshare.com/files/2297918"], "description"=>"<div><p><i>Pseudomonas aeruginosa</i> is the causative agent of chronic respiratory infections and is an important pathogen of cystic fibrosis patients. Adaptive mutations play an essential role for antimicrobial resistance and persistence. The factors that contribute to bacterial mutagenesis in this environment are not clear. Recently it has been proposed that cationic antimicrobial peptides such as LL-37 could act as mutagens in <i>P</i>. <i>aeruginosa</i>. Here we provide experimental evidence that mutagenesis is the product of a joint action of LL-37 and free iron. By estimating mutation rate, mutant frequencies and assessing mutational spectra in <i>P</i>. <i>aeruginosa</i> treated either with LL-37, iron or a combination of both we demonstrate that mutation rate and mutant frequency were increased only when free iron and LL-37 were present simultaneously. Colistin had the same effect. The addition of an iron chelator completely abolished this mutagenic effect, suggesting that LL-37 enables iron to enter the cells resulting in DNA damage by Fenton reactions. This was also supported by the observation that the mutational spectrum of the bacteria under LL-37-iron regime showed one of the characteristic Fenton reaction fingerprints: C to T transitions. Free iron concentration in nature and within hosts is kept at a very low level, but the situation in infected lungs of cystic fibrosis patients is different. Intermittent bleeding and damage to the epithelial cells in lungs may contribute to the release of free iron that in turn leads to generation of reactive oxygen species and deterioration of the respiratory tract, making it more susceptible to the infection.</p></div>", "links"=>[], "tags"=>["fibrosis patients", "Free iron concentration", "mutation rate", "Reactive oxygen species", "cationic antimicrobial peptides", "dna", "Bacteria Pseudomonas aeruginosa", "ll", "Fenton reaction fingerprints"], "article_id"=>1563559, "categories"=>["Uncategorised"], "users"=>["Alexandro Rodríguez-Rojas", "Olga Makarova", "Uta Müller", "Jens Rolff"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005546.s001", "https://dx.doi.org/10.1371/journal.pgen.1005546.s002", "https://dx.doi.org/10.1371/journal.pgen.1005546.s003", "https://dx.doi.org/10.1371/journal.pgen.1005546.s004", "https://dx.doi.org/10.1371/journal.pgen.1005546.s005", "https://dx.doi.org/10.1371/journal.pgen.1005546.s006", "https://dx.doi.org/10.1371/journal.pgen.1005546.s007", "https://dx.doi.org/10.1371/journal.pgen.1005546.s008", "https://dx.doi.org/10.1371/journal.pgen.1005546.s009", "https://dx.doi.org/10.1371/journal.pgen.1005546.s010", "https://dx.doi.org/10.1371/journal.pgen.1005546.s011"], "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cationic_Peptides_Facilitate_Iron_induced_Mutagenesis_in_Bacteria_/1563559", "title"=>"Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-02 04:10:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297890"], "description"=>"<p>Distribution of the mutations in the 1160 bp-long fragment of <i>glpT</i> in <i>P</i>. <i>aeruginosa</i> PA14 fosfomycin-resistant clones treated with iron, LL-37, or a combination of both. The number of mutations (nucleotide substitutions, indels) is plotted against respective nucleotide positions within the gene fragment. Note the overlapping mutations at positions 220–225, 409 and 524 bp in iron and LL-37 treatments and absence of common mutations in LL-37+Fe<sup>2+</sup> treatment. The fig was generated using the mutational spectrum analysis software iMARS [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005546#pgen.1005546.ref039\" target=\"_blank\">39</a>].</p>", "links"=>[], "tags"=>["fibrosis patients", "Free iron concentration", "mutation rate", "Reactive oxygen species", "cationic antimicrobial peptides", "dna", "Bacteria Pseudomonas aeruginosa", "ll", "Fenton reaction fingerprints"], "article_id"=>1563548, "categories"=>["Uncategorised"], "users"=>["Alexandro Rodríguez-Rojas", "Olga Makarova", "Uta Müller", "Jens Rolff"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005546.g004", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutation_hotspots_in_glpT_/1563548", "title"=>"Mutation hotspots in <i>glpT</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 04:10:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297887"], "description"=>"<p>This supports the notion that iron is causal in increasing mutagenesis (A). In the same line, over-expression of Dps, a natural iron chelator in bacteria, also decreases the mutant frequency to rifampicin (B). Error bars represent 95% confidence intervals for mutant frequencies.</p>", "links"=>[], "tags"=>["fibrosis patients", "Free iron concentration", "mutation rate", "Reactive oxygen species", "cationic antimicrobial peptides", "dna", "Bacteria Pseudomonas aeruginosa", "ll", "Fenton reaction fingerprints"], "article_id"=>1563545, "categories"=>["Uncategorised"], "users"=>["Alexandro Rodríguez-Rojas", "Olga Makarova", "Uta Müller", "Jens Rolff"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005546.g002", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_mutagenesis_of_LL_37_Fe_2_combination_is_suppressed_by_the_addition_of_an_iron_chelator_/1563545", "title"=>"The mutagenesis of LL-37+Fe<sup>2+</sup> combination is suppressed by the addition of an iron chelator.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 04:10:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297886"], "description"=>"<p>No changes occur when LL-37 or iron are added to the culture separately. Error bars represent 95% confidence intervals for mutation rates.</p>", "links"=>[], "tags"=>["fibrosis patients", "Free iron concentration", "mutation rate", "Reactive oxygen species", "cationic antimicrobial peptides", "dna", "Bacteria Pseudomonas aeruginosa", "ll", "Fenton reaction fingerprints"], "article_id"=>1563544, "categories"=>["Uncategorised"], "users"=>["Alexandro Rodríguez-Rojas", "Olga Makarova", "Uta Müller", "Jens Rolff"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005546.g001", "stats"=>{"downloads"=>11, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_joint_action_of_LL_37_and_ferrous_iron_induces_an_increase_in_the_mutation_rate_of_P_aeruginosa_/1563544", "title"=>"The joint action of LL-37 and ferrous iron induces an increase in the mutation rate of <i>P</i>. <i>aeruginosa</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 04:10:51"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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