Genetic mechanisms of Coxiella burnetii lipopolysaccharide phase variation
Publication Date
February 26, 2018
Authors
Paul A. Beare, Brendan M. Jeffrey, Carrie M. Long, Craig M. Martens, et al
Volume
14
Issue
3
Pages
e1006922
DOI
https://dx.plos.org/10.1371/journal.ppat.1006922
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006922
Scopus
85042694569
Mendeley
http://www.mendeley.com/research/genetic-mechanisms-coxiella-burnetii-lipopolysaccharide-phase-variation
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Mendeley | Further Information

{"title"=>"Genetic mechanisms of Coxiella burnetii lipopolysaccharide phase variation", "type"=>"journal", "authors"=>[{"first_name"=>"Paul A.", "last_name"=>"Beare", "scopus_author_id"=>"55889445500"}, {"first_name"=>"Brendan M.", "last_name"=>"Jeffrey", "scopus_author_id"=>"25824982200"}, {"first_name"=>"Carrie M.", "last_name"=>"Long", "scopus_author_id"=>"57193568014"}, {"first_name"=>"Craig M.", "last_name"=>"Martens", "scopus_author_id"=>"57200969752"}, {"first_name"=>"Robert A.", "last_name"=>"Heinzen", "scopus_author_id"=>"7004635652"}], "year"=>2018, "source"=>"PLoS Pathogens", "identifiers"=>{"doi"=>"10.1371/journal.ppat.1006922", "sgr"=>"85042694569", "pui"=>"620981845", "scopus"=>"2-s2.0-85042694569", "issn"=>"15537374", "isbn"=>"1111111111"}, "id"=>"bfe5f0c9-8f12-3d95-a8b7-51c19ead9bd2", "abstract"=>"Coxiella burnetii is an intracellular pathogen that causes human Q fever, a disease that normally presents as a severe flu-like illness. Due to high infectivity and disease severity, the pathogen is considered a risk group 3 organism. Full-length lipopolysaccharide (LPS) is required for full virulence and disease by C. burnetii and is the only virulence factor currently defined by infection of an immunocompetent animal. Transition of virulent phase I bacteria with smooth LPS, to avirulent phase II bacteria with rough LPS, occurs during in vitro passage. Semi-rough intermediate forms are also observed. Here, the genetic basis of LPS phase conversion was investigated to obtain a more complete understanding of C. burnetii pathogenesis. Whole genome sequencing of strains producing intermediate and/or phase II LPS identified several common mutations in predicted LPS biosynthesis genes. After passage in broth culture for 30 weeks, phase I strains from different genomic groups exhibited similar phase transition kinetics and elevation of mutations in LPS biosynthesis genes. Targeted mutagenesis and genetic complementation using a new C. burnetii nutritional selection system based on lysine auxotrophy confirmed that six of the mutated genes were necessary for production of phase I LPS. Disruption of two of these genes in a C. burnetii phase I strain resulted in production of phase II LPS, suggesting inhibition of the encoded enzymes could represent a new therapeutic strategy for treatment of Q fever. Additionally, targeted mutagenesis of genes encoding LPS biosynthesis enzymes can now be used to construct new phase II strains from different genomic groups for use in pathogen-host studies at a risk group 2 level.", "link"=>"http://www.mendeley.com/research/genetic-mechanisms-coxiella-burnetii-lipopolysaccharide-phase-variation", "reader_count"=>10, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Student > Ph. D. Student"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1, "Student > Ph. D. Student"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>6, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}

Scopus | Further Information

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