The pathogenic properties of a novel and conserved gene product, KerV, in proteobacteria
Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the...
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Published in | PloS one Vol. 4; no. 9; p. e7167 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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25.09.2009
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Abstract | Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design. |
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AbstractList | Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design. Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia , Escherichia , Shigella , Vibrio , Salmonella , Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design. |
Audience | Academic |
Author | Baldini, Regina L Goumnerov, Boyan C Rahme, Laurence G Boechat, Ana Laura Apidianakis, Yiorgos An, Dingding |
AuthorAffiliation | Baylor College of Medicine, United States of America 4 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil 3 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America 1 Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America 2 Shriners Research Institute, Boston, Massachusetts, United States of America |
AuthorAffiliation_xml | – name: Baylor College of Medicine, United States of America – name: 1 Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America – name: 3 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America – name: 2 Shriners Research Institute, Boston, Massachusetts, United States of America – name: 4 Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil |
Author_xml | – sequence: 1 givenname: Dingding surname: An fullname: An, Dingding organization: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America – sequence: 2 givenname: Yiorgos surname: Apidianakis fullname: Apidianakis, Yiorgos – sequence: 3 givenname: Ana Laura surname: Boechat fullname: Boechat, Ana Laura – sequence: 4 givenname: Regina L surname: Baldini fullname: Baldini, Regina L – sequence: 5 givenname: Boyan C surname: Goumnerov fullname: Goumnerov, Boyan C – sequence: 6 givenname: Laurence G surname: Rahme fullname: Rahme, Laurence G |
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CitedBy_id | crossref_primary_10_1371_journal_pone_0177825 crossref_primary_10_1016_j_biomaterials_2022_121613 crossref_primary_10_1016_j_meegid_2011_04_029 crossref_primary_10_3402_jom_v4i0_10368 crossref_primary_10_1111_mmi_14819 crossref_primary_10_1126_sciadv_abf0677 crossref_primary_10_3389_fcimb_2020_00214 crossref_primary_10_3389_fmicb_2022_963260 crossref_primary_10_4161_viru_27524 crossref_primary_10_1128_CMR_00084_16 crossref_primary_10_3390_pathogens2020209 |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: DA YA RLB LR. Performed the experiments: DA YA ALB RLB BCG. Analyzed the data: DA YA ALB RLB BCG LR. Contributed reagents/materials/analysis tools: DA YA RLB BCG LR. Wrote the paper: DA YA RLB LR. |
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SubjectTerms | Amoeba Animal models Animals Anti-Bacterial Agents - pharmacology Antibacterial agents Antibiotics Arabidopsis Arabidopsis - microbiology Bacteria Bacterial infections Bacterial Proteins - metabolism Bioinformatics Burkholderia Cholera Cholera toxin Computational Biology - methods Conserved Sequence Deoxyribonucleic acid Detoxification DNA DNA biosynthesis DNA repair DNA replication Drosophila melanogaster Drosophila melanogaster - metabolism Drug development Enzymes Epigenetics Gene expression Gene Expression Regulation, Bacterial Genomes Health aspects Humans Infection Infections Infectious Diseases/Bacterial Infections Insects Medical schools Methyltransferase Methyltransferases - genetics Methyltransferases - physiology Mice Microbiology Microbiology/Cellular Microbiology and Pathogenesis Mutants Pathogenesis Pathogens Phylogeny Plants (botany) Proteins Proteobacteria - metabolism Pseudomonas aeruginosa Pseudotuberculosis Salmonella Surgery Transferases Vibrio cholerae - metabolism Virulence Virulence (Microbiology) Virulence factors Virulence Factors - metabolism Waterborne diseases Yersinia Yersinia enterocolitica Yersinia pseudotuberculosis Yersinia pseudotuberculosis - metabolism |
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Title | The pathogenic properties of a novel and conserved gene product, KerV, in proteobacteria |
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