ArticleMolecular microbiology2012
NaxD is a deacetylase required for lipid A modification and Francisella pathogenesis.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
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- Constitutive Phenotypic Modification of Lipid A in Clinical Acinetobacter baumannii Isolates.Microbiology spectrum · 2022Article
- Molecular engineering of antimicrobial peptides: microbial targets, peptide motifs and translation opportunities.Biophysical reviews · 2021Review
- Genetic Determinants of Antibiotic Resistance inFrontiers in microbiology · 2021Review
- Catalytically Active Cas9 Mediates Transcriptional Interference to Facilitate Bacterial Virulence.Molecular cell · 2019Article
- Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment.Scientific reports · 2019Article
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- Comparative NanoUPLC-MSScientific reports · 2017Article
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- Polymyxin: Alternative Mechanisms of Action and Resistance.Cold Spring Harbor perspectives in medicine · 2016Review
- Bacterial strategies of resistance to antimicrobial peptides.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- Potentiation ofMedChemComm · 2016Article
- A PmrB-Regulated Deacetylase Required for Lipid A Modification and Polymyxin Resistance in Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2015Article
- On the in vivo significance of bacterial resistance to antimicrobial peptides.Biochimica et biophysica acta · 2015Review
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Authors and funding
13 authors at 9 institutions in 1 country.
Funding
Abstract
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.
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