Structure of the Lipopolysaccharide from <i>Paenalcaligenes hominis</i>: A Chemical Perspective on Immune Recognition
Gram-negative bacterium <i>Paenalcaligenes hominis</i>, which is increasingly prevalent in elderly individuals, is associated with cognitive decline and gut-brain axis dysfunction. Here, we present a comprehensive structural characterization of <i>P. hominis</i> lipopolysaccharide (LPS), a key modulator of immune recognition and the main component of its outer membrane. Using a multidisciplinary approach combining chemical, spectroscopic, spectrometric, biophysical and computational methods, we unveil a unique O-antigen characterized by a trisaccharide repeating unit containing rhamnose and glucosamine, displaying nonstoichiometric O-acetylation and a terminal methylated rhamnose capping the saccharide chain. Furthermore, we disclose a short core oligosaccharide and a Lipid A composed of penta- to tetra-acylated species. Notably, this LPS exhibits reduced activation of Toll-Like Receptor-dependent signaling compared to the highly immunostimulatory <i>Escherichia coli</i> LPS and elicits a poor pro-inflammatory cytokine response. Moreover, <i>P. hominis</i> LPS exhibits selective binding to immune lectins such as Ficolin-3 and Galectin-4, as shown by the microarray assays. This raises the possibility that lectin-mediated recognition may represent an alternative route of immune engagement, which could help explain altered immune responses observed in elderly individuals. These findings provide a molecular basis for further exploring the role of <i>P. hominis</i> LPS in microbiota-induced immune modulation and its possible impact on age-related inflammatory and neurodegenerative conditions.
Authors
- Flaviana Di Lorenzo (ORCID: https://orcid.org/0000-0003-4821-0114)
- Adele Vanacore
- Emanuela Andretta (ORCID: https://orcid.org/0000-0002-4402-0914)
- Marcello Mercogliano (ORCID: https://orcid.org/0000-0001-7871-372X)
- Luigi Paduano (ORCID: https://orcid.org/0000-0002-1105-4237)
- Giuseppe Vitiello (ORCID: https://orcid.org/0000-0003-3389-6942)
- Giovanni Smaldone (ORCID: https://orcid.org/0000-0002-1989-4740)
- Cristina Di Carluccio (ORCID: https://orcid.org/0000-0001-5895-9829)
- Antonio Molinaro (ORCID: https://orcid.org/0000-0002-3456-7369)
- María Asunción Campanero‐Rhodes (ORCID: https://orcid.org/0000-0002-3373-0064)
- Dolores Solı́s (ORCID: https://orcid.org/0000-0002-8148-1875)
- Lorena Buono
- Giovanni Pecoraro (ORCID: https://orcid.org/0000-0001-6622-4208)
- Ferran Nieto‐Fabregat (ORCID: https://orcid.org/0000-0001-9847-3030)
- Alba Silipo (ORCID: https://orcid.org/0000-0002-5394-6532)
- Luke A. Clifton (ORCID: https://orcid.org/0000-0001-8754-362X)
- Alessandro Cangiano
- Dong‐Hyun Kim (ORCID: https://orcid.org/0000-0003-4783-7900)
- Jeon-Kyung Kim
Institutions
- Science and Technology Facilities Council (GB)
- Kyung Hee University (KR)
- Consorzio Interuniversitario per lo Sviluppo dei Sistemi a Grande Interfase (IT)
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES)
- CEINGE Biotecnologie Avanzate Franco Salvatore (Italy) (IT)
- University of Naples Federico II (IT)
Publication Details
- Journal
- JACS Au
- Published
- 2025-06-24
- DOI
- https://doi.org/10.1021/jacsau.5c00441
- Citations
- 3
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- Ministerio de Ciencia, Innovación y Universidades
- Ministero della Salute
- Ministero degli Affari Esteri e della Cooperazione Internazionale
- Ministero dell'Università e della Ricerca
- Instituto de Salud Carlos III
- European Regional Development Fund
- European Social Fund
- H2020 European Research Council
- HORIZON EUROPE European Research Council