Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy
Publication Date
September 15, 2016
Journal
PLOS Biology
Authors
Dilay Hazal Ayhan, Yusuf Talha Tamer, Mohammed Akbar, Stacey M. Bailey, et al
Volume
14
Issue
9
Pages
e1002552
DOI
http://doi.org/10.1371/journal.pbio.1002552
Publisher URL
http://journals.plos.org/plosbiology/article?id=10.1371%2Fjournal.pbio.1002552
Scopus
84992109011
Mendeley
http://www.mendeley.com/research/sequencespecific-targeting-bacterial-resistance-genes-increases-antibiotic-efficacy
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Mendeley | Further Information

{"title"=>"Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy", "type"=>"journal", "authors"=>[{"first_name"=>"Dilay Hazal", "last_name"=>"Ayhan", "scopus_author_id"=>"56996026900"}, {"first_name"=>"Yusuf Talha", "last_name"=>"Tamer", "scopus_author_id"=>"55909767100"}, {"first_name"=>"Mohammed", "last_name"=>"Akbar", "scopus_author_id"=>"8950164400"}, {"first_name"=>"Stacey M.", "last_name"=>"Bailey", "scopus_author_id"=>"57191608669"}, {"first_name"=>"Michael", "last_name"=>"Wong", "scopus_author_id"=>"56403802700"}, {"first_name"=>"Seth M.", "last_name"=>"Daly", "scopus_author_id"=>"57191622831"}, {"first_name"=>"David E.", "last_name"=>"Greenberg", "scopus_author_id"=>"26660637300"}, {"first_name"=>"Erdal", "last_name"=>"Toprak", "scopus_author_id"=>"13205703700"}], "year"=>2016, "source"=>"PLoS Biology", "identifiers"=>{"sgr"=>"84992109011", "doi"=>"10.1371/journal.pbio.1002552", "issn"=>"15457885", "pui"=>"612818700", "isbn"=>"10.1371/journal.pbio.1002552", "pmid"=>"27631336", "scopus"=>"2-s2.0-84992109011"}, "id"=>"889d486b-455f-30ee-bc11-dde3ae7a1364", "abstract"=>"The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities.", "link"=>"http://www.mendeley.com/research/sequencespecific-targeting-bacterial-resistance-genes-increases-antibiotic-efficacy", "reader_count"=>64, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>15, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>13, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>15, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>2, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>13, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>13, "Agricultural and Biological Sciences"=>30, "Medicine and Dentistry"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>4, "Physics and Astronomy"=>2, "Chemistry"=>3, "Computer Science"=>1, "Immunology and Microbiology"=>2, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>4}}, "reader_count_by_country"=>{"China"=>1, "Estonia"=>1}, "group_count"=>2}

Scopus | Further Information

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