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 inPloS one Vol. 4; no. 9; p. e7167
Main Authors An, Dingding, Apidianakis, Yiorgos, Boechat, Ana Laura, Baldini, Regina L, Goumnerov, Boyan C, Rahme, Laurence G
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 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.
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
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– 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
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  surname: An
  fullname: An, Dingding
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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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SSID ssj0053866
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Snippet Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we...
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Open Access Repository
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StartPage e7167
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
URI https://www.ncbi.nlm.nih.gov/pubmed/19779606
https://www.proquest.com/docview/1292231115
https://search.proquest.com/docview/734059603
https://pubmed.ncbi.nlm.nih.gov/PMC2744870
https://doaj.org/article/69db46a8d5ef4d97af4c74bfe97b6f83
http://dx.doi.org/10.1371/journal.pone.0007167
Volume 4
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