Bradyrhizobium Lipid A: Immunological Properties and Molecular Basis of Its Binding to the Myeloid Differentiation Protein-2/Toll-Like Receptor 4 Complex

Abstract

Lipopolysaccharides (LPS) are potent activator of the innate immune response through the binding to the myeloid differentiation protein-2 (MD-2)/toll-like receptor 4 (TLR4) receptor complexes. Although a variety of LPSs have been characterized so far, a detailed molecular description of the structure–activity relationship of the lipid A part has yet to be clarified. Photosynthetic Bradyrhizobium strains, symbiont of Aeschynomene legumes, express distinctive LPSs bearing very long-chain fatty acids with a hopanoid moiety covalently linked to the lipid A region. Here, we investigated the immunological properties of LPSs isolated from Bradyrhizobium strains on both murine and human immune systems. We found that they exhibit a weak agonistic activity and, more interestingly, a potent inhibitory effect on MD-2/TLR4 activation exerted by toxic enterobacterial LPSs. By applying computational modeling techniques, we also furnished a plausible explanation for the Bradyrhizobium LPS inhibitory activity at atomic level, revealing that its uncommon lipid A chemical features could impair the proper formation of the receptorial complex, and/or has a destabilizing effect on the pre-assembled complex itself.

Fucosylated oligosaccharide Lacto-N-fucopentaose I ameliorates enterovirus 71 infection by inhibiting apoptosis

“…Dactylosporangium produced trans -4-hydroxy-proline through genetic engineering technology to inhibit the development of inflammation ( Zhang et al, 2019 ). Bradyrhizobium had good immunological activity and inhibited the expression of inflammatory receptor TLR4 both in vivo and in vitro ( Lembo-Fazio et al, 1888 ). Together, bacteria degrade many substances such as alkaloids and polysaccharides to increase the lifespan of nematodes in C. elegans (Zhang et al, 2017; Chen et al, 2020).…”

Pairing Bacteroides vulgatus LPS Structure with Its Immunomodulatory Effects on Human Cellular Models

“…BMDMs were derived from the bone marrow cells collected from 5 week old female mice, as already reported. 39 Animal studies were conducted according to protocols approved by the University of Rome La Sapienza and adhered strictly to the Italian Ministry of Health guidelines for the use and care of experimental animals. BMDMs were differentiated during 7 days in RPMI 1640 (Lonza), supplemented with 10% of heat-inactivated FBS (HycloneTM, Euroclone), 1% of l -glutamine (Lonza), 1% sodium pyruvate (Lonza), 1% NEAA (Lonza), 0.5% 2-ME (Gibco), and 40 ng/mL macrophage colony-stimulating factor (M-CSF; Miltenyi Biotec).…”

Collagen Peptides Isolated from Salmo salar and Tilapia nilotica Skin Accelerate Wound Healing by Altering Cutaneous Microbiome Colonization via Upregulated NOD2 and BD14

“…Stenotrophomonas , Bradyrhizobium , Sphingomonas , and Phyllobacterium bacteria were highly abundant in the MC group with low toxicity but can lead to human infection with severe immunodeficiency. They could all secrete lipopolysaccharides (LPS) − except Sphingomonas . LPS is one of the most potent inflammatory chemicals, acting on the Toll-like receptor (TLR-4) to induce the expression of inflammatory genes.…”

“…We supposed that the Stenotrophomonas , Bradyrhizobium , and Phyllobacterium may be directly linked to inflammation promotion. Previous studies showed that the Stenotrophomonas , Bradyrhizobium , and Phyllobacterium all secrete LPS. − LPS could induce the production of proinflammatory cytokine mediators such as NO, IL-6, and TNF-α and inhibit the secretion of IL-10 . It also could activate the NF-κB pathway via NOD2 gene expression. , LPS from Stenotrophomonas , Bradyrhizobium , and Phyllobacterium is a virulence factor involved in cell colonization and the resistance of immune induced-cell damage against macrophages or antibiotics, stimulating the production of TNF-α, inducing the expression of IL-8, and secreting lipid A to activate the innate immune response of the host. ,, Sphingomonas were highly abundant in MC and lack the LPS and endotoxin activity, and they can form strong biofilms against the macrophages of the host dental ulcer wound .…”