ArticleInfection and immunity2014
Phosphoethanolamine decoration of Neisseria gonorrhoeae lipid A plays a dual immunostimulatory and protective role during experimental genital tract infection.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 43 citations in OpenAlex.
- Neutrophil CEACAMs and the Inflammatory Response toJournal of innate immunity · 2026Review
- Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
- Vertebrate and Invertebrate Animal and New In Vitro Models for StudyingPathogens (Basel, Switzerland) · 2023Review
- Commensal Neisseria species share immune suppressive mechanisms with Neisseria gonorrhoeae.PloS one · 2023Article
- Novel small molecules that increase the susceptibility of Neisseria gonorrhoeae to cationic antimicrobial peptides by inhibiting lipid A phosphoethanolamine transferase.The Journal of antimicrobial chemotherapy · 2022Article
- Progesterone SuppressesFrontiers in microbiology · 2021Article
- Predominant phosphorylation patterns inJournal of lipid research · 2020Article
- Identification of aPathogens (Basel, Switzerland) · 2020Article
- Substrate structure-activity relationship reveals a limited lipopolysaccharide chemotype range for intestinal alkaline phosphatase.The Journal of biological chemistry · 2019Article
- Biological feasibility and importance of a gonorrhea vaccine for global public health.Vaccine · 2019Review
- Pharmacokinetic Data Are Predictive ofAntimicrobial agents and chemotherapy · 2019Article
- Article
- The Pathogenic Neisseria Use a Streamlined Set of Peptidoglycan Degradation Proteins for Peptidoglycan Remodeling, Recycling, and Toxic Fragment Release.Frontiers in microbiology · 2019Review
- Quantitative Proteomics of the 2016 WHOMolecular & cellular proteomics : MCP · 2019Article
- Gonococcal Defenses against Antimicrobial Activities of Neutrophils.Trends in microbiology · 2018Review
- Human Antimicrobial Peptides in Bodily Fluids: Current Knowledge and Therapeutic Perspectives in the Postantibiotic Era.Medicinal research reviews · 2018Review
- Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting.Frontiers in microbiology · 2018Review
- Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: neutrophilic host response, sustained infection, and clinical sequelae.Current opinion in hematology · 2018Review
- Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection.Infection and immunity · 2017Article
- Control ofmBio · 2017Article
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9 authors at 4 institutions in 1 country.
Funding
Abstract
The induction of an intense inflammatory response by Neisseria gonorrhoeae and the persistence of this pathogen in the presence of innate effectors is a fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A increases gonococcal resistance to complement-mediated bacteriolysis and cationic antimicrobial peptides (CAMPs), and recently we reported that wild-type N. gonorrhoeae strain FA1090 has a survival advantage relative to a PEA transferase A (lptA) mutant in the human urethral-challenge and murine lower genital tract infection models. Here we tested the immunostimulatory role of this lipid A modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an lptA mutant of strain FA19 induced significantly lower levels of NF-κB in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in female mice infected with the isogenic lptA mutant, in contrast to mice infected with the wild-type and complemented lptA mutant bacteria. We also demonstrated that lptA mutant bacteria were more susceptible to human and murine cathelicidins due to increased binding by these peptides and that the differential induction of NF-κB by wild-type and unmodified lipid A was more pronounced in the presence of CAMPs. This work demonstrates that PEA decoration of lipid A plays both protective and immunostimulatory roles and that host-derived CAMPs may further reduce the capacity of PEA-deficient lipid A to interact with TLR4 during infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.