Taxonomic group: bacteria / Proteobacteria (Phylum: Proteobacteria)
Associated disease: infection due to Escherichia coli [ICD11: XN6P4 ]
 
NCBI PubMed ID: 22966934
Publication DOI: 10.1111/mmi.12004
Journal NLM ID: 8712028
Publisher: Blackwell Publishing
Correspondence: david.weissemory.edu
Institutions: Department of Microbiology and Immunology, Microbiology and Molecular Genetics Program, Emory University, Atlanta, GA, USA, Emory Vaccine Center, Emory University, Atlanta, GA, USA, Department of Biochemistry, Duke University Medical Center, Durham, NC, USA, Department of Microbiology, Immunology, and Biochemistry, The University of Tennessee Health Science Center, Memphis, TN, USA, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, Department of Biology, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA, Veterans Affairs Medical Center, Decatur, GA, USA, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA, USA

Modification of specific Gram-negative bacterial cell envelope components, such as capsule, O-antigen and lipid A, are often essential for the successful establishment of infection. Francisella species express lipid A molecules with unique characteristics involved in circumventing host defences, which significantly contribute to their virulence. In this study, we show that NaxD, a member of the highly conserved YdjC superfamily, is a deacetylase required for an important modification of the outer membrane component lipid A in Francisella. Mass spectrometry analysis revealed that NaxD is essential for the modification of a lipid A phosphate with galactosamine in Francisella novicida, a model organism for the study of highly virulent Francisella tularensis. Significantly, enzymatic assays confirmed that this protein is necessary for deacetylation of its substrate. In addition, NaxD was involved in resistance to the antimicrobial peptide polymyxin B and critical for replication in macrophages and in vivo virulence. Importantly, this protein is also required for lipid A modification in F. tularensis as well as Bordetella bronchiseptica. Since NaxD homologues are conserved among many Gram-negative pathogens, this work has broad implications for our understanding of host subversion mechanisms of other virulent bacteria.

Pathogenesis, virulence, lipid A, Francisella tularensis, vaccine, cell envelope, molecular genetics, outer membrane, macrophages

Structure type: oligomer
Location inside paper: p.612, fig.1A
Compound class: LPS, lipid A
Contained glycoepitopes: IEDB_130650,IEDB_130658,IEDB_130659,IEDB_135394,IEDB_135515,IEDB_141807,IEDB_150908,IEDB_151531,IEDB_176772,IEDB_534864
 
Methods: ESI-MS, MS/MS, genetic methods, biochemical methods, statistical analysis, LC-MS
Comments, role: LPS
 
Related record ID(s): 27233, 28445
NCBI Taxonomy refs (TaxIDs): 562
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