Lipopolysaccharide (LPS) is well known for its immunostimulatory activity and its contribution to the permeability barrier of the Gram-negative outer membrane. Yet LPS is essential for growth in nearl...

Publication date: Available online 24 October 2026 Source: Journal of Proteomics Author(s): Tatiana Maurício, Bruno M. Neves, M. Rosário Domingues, Pedro Domingues

Caspase-11 (Casp11) is a murine zymogen that becomes active upon sensing cytosolic lipopolysaccharide (LPS), enabling it to form the non-canonical inflammasome and execute an inflammatory cell death k...

Iron transport and heme synthesis are essential processes in human metabolism, and any dysregulation in these mechanisms, such as inflammation, can have deleterious effects. Lipopolysaccharide (LPS)-i...

Read the full paper: Activating systemic inflammation with lipopolysaccharide drives microglia-mediated degradation of perineuronal nets after cervical spinal cord injury in female rats

Dysregulation of nucleus pulposus cells (NPCs) is a critical contributor to intervertebral disc degeneration (IDD). One characteristic of degenerated discs is the increased apoptosis of NPCs and the substantial degradation of the extracellular matrix (ECM). This study identified significantly reduced miR-204-5p levels in IDD tissues. Using lipopolysaccharide (LPS)-treated rat NPCs, miR-204-5p overexpression was found to suppress apoptosis, reduce ECM degradation, and enhance ECM synthesis. Me...

While lysosomes are typically globular in morphology, lipopolysaccharide-activated macrophages reorganize lysosomes into an expanded tubular network. Here, we sought to determine if the V-ATPase and t...

Structures of the protein machinery in Gram-negative bacteria that transports lipopolysaccharide (LPS) from the cytoplasmic membrane to the outer leaflet of the outer membrane reveal how conformational changes in response to the presence of LPS promote its transport.

Structures of the protein machinery in Gram-negative bacteria that transports lipopolysaccharide (LPS) from the cytoplasmic membrane to the outer leaflet of the outer membrane reveal how conformationa...

Structures of the protein machinery in Gram-negative bacteria that transports lipopolysaccharide (LPS) from the cytoplasmic membrane to the outer leaflet of the outer membrane reveal how conformational changes in response to the presence of LPS promote its transport.

No statistical methods were used to predetermine sample size. Experiments were not randomized, and investigators were not blinded to allocation during experiments and outcome assessment. For development and verification of ΔlptC, ΔlptA and ΔlptCΔlptA strains complemented with the LptC–LptA fusion protein (carried on the plasmid pBAD18-LptCA-His), four independent isolates of each strain were phenotypically characterized. After confirming that all selected isolates behaved the same phenotypically, one of them was kept after confirming by PCR (Extended Data Fig. 1b) that it had the expected chromosomal alleles. All ATP hydrolysis measurements (Fig. 3f,g and Extended Data Fig. 1f) were made as three independent measurements unless otherwise indicated in the figure legend; data are reported as mean ± s.d. ATP binding measurements (Fig. 3a,b,e) were made as three independent measurements; data are reported as mean ± s.d. Source data files are provided for all ATP hydrolysis and ATP binding measurements. All western blot data shown are representative of at least three independent replicates that produced similar results (Figs. 2e, 4a–c,e–g and 5b,c and Extended Data Figs. 1d,e and 7a–d). Representative electron micrographs (Fig. 1b and Extended Data Figs. 2c, 4c, 5c, 6c and 8c) were chosen to contain approximately the median number of...

Cell surface lipoproteins (SLPs) play crucial roles in the pathogenesis and cell biology of gram-negative bacteria, yet the route by which they reach the cell surface has remained unknown except in special cases. Here we show that in Bacteroidota bacteria, a phylum that includes prominent human commensals and anaerobic pathogens, SLP export is carried out by the outer membrane lipopolysaccharide (LPS) translocon. Isolation and structural characterisation of LPS translocon complexes from two Bacteroidota species reveals that they are massively enlarged and elaborated relative to the Escherichia coli paradigm with up to eight additional subunits located within, and on either side of, the outer membrane. We establish a role for the universally conserved core LptD subunit and four of the additional Bacteroidota-specific subunits in SLP export. Expansion of the LPS translocon in the Bacteroidota may allow export of the unusually complex SLPs found in this phylum. Our discoveries raise the possibility that SLP export is a conserved second function of the LPS transport pathway across gram-negative bacteria. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 101201241, 833713 Wellcome Trust, 317933/Z/24/Z St. Jude Children's Research Hospital, https://ror.org/02r3e0967

The selection of appropriate in vitro inflammatory models is critical for mechanistic studies of neuroinflammation and the screening of anti-inflammatory therapeutics. Lipopolysaccharide (LPS) combine...

Read the full paper: Acute lipopolysaccharide (LPS) treatment in male mice exacerbates dextroamphetamine-induced hyperlocomotion without detectable changes in nucleus accumbens dopaminergic activity

Patients with severe dengue virus (DENV) infection can experience hemorrhage, shock and organ damage that coincides with defervescence and declining viremia. In addition to vascular leak, published work has shown that gut barrier permeability and elevated serum lipopolysaccharide (LPS) levels correlate with DENV disease severity. We previously described profound gut pathology in a mouse model of infection. This led to the hypothesis that a loss of gut epithelial barrier integrity and the influx of microbial products contribute to exacerbated inflammation and severe dengue disease. Consistent with this, here we demonstrated that DENV2 infection of AG129 mice compromised the gut epithelial barrier, promoted bacterial translocation, and induced microbial changes indicative of dysbiosis, including a reduced abundance of putatively beneficial microbial taxa and disrupted microbial circadian oscillations. Depleting gut bacteria with antibiotics from 1-day post-infection sharply reduced gut pathology as well as viral RNA in the proximal colon and liver, and the number of infected Kupffer cells in the liver. There was no evidence for systemic suppression of viral replication. We propose that viral infection of intestinal macrophages leads to inflammatory damage and mucosal barrier breakdown, dysbiosis and gut leak, with gut bacteria-dependent products promoting the susceptibility of Kupffer cells to DENV infection. Given the importance of liver damage in severe and fatal dengue disease, therapies that protect the gut barrier may help reduce disease severity.

Patients with severe dengue virus (DENV) infection can experience hemorrhage, shock and organ damage that coincides with defervescence and declining viremia. In addition to vascular leak, published work has shown that gut barrier permeability and elevated serum lipopolysaccharide (LPS) levels correlate with DENV disease severity. We previously described profound gut pathology in a mouse model of infection. This led to the hypothesis that a loss of gut epithelial barrier integrity and the influx of microbial products contribute to exacerbated inflammation and severe dengue disease. Consistent with this, here we demonstrated that DENV2 infection of AG129 mice compromised the gut epithelial barrier, promoted bacterial translocation, and induced microbial changes indicative of dysbiosis, including a reduced abundance of putatively beneficial microbial taxa and disrupted microbial circadian oscillations. Depleting gut bacteria with antibiotics from 1-day post-infection sharply reduced gut pathology as well as viral RNA in the proximal colon and liver, and the number of infected Kupffer cells in the liver. There was no evidence for systemic suppression of viral replication. We propose that viral infection of intestinal macrophages leads to inflammatory damage and mucosal barrier breakdown, dysbiosis and gut leak, with gut bacteria-dependent products promoting the susceptibility of Kupffer cells to DENV infection. Given the importance of liver damage in severe and fatal dengue disease, therapies that protect the gut barrier may help reduce disease severity.