Modifications of Bordetella bronchiseptica core lipopolysaccharide influence immune response without affecting protective activity.

Bioorg Med Chem Lett

Instituto de Biotecnología y Biología Molecular, CCT La Plata CONICET, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Calles 47 y 115, 1900 La Plata, Argentina.

Published: February 2017

Bordetella bronchiseptica produces respiratory disease primarily in mammals including humans. Although a considerably amount of research has been generated regarding lipopolysaccharide (LPS) role during infection and stimulating innate and adaptive immune response, mechanisms involved in LPS synthesis are still unknown. In this context we searched in B. bronchiseptica genome for putative glycosyltransferases. We found possible genes codifying for enzymes involved in sugar substitution of the LPS structure. We decided to analyse BB3394 to BB3400 genes, closed to a previously described LPS biosynthetic locus in B. pertussis. Particularly, conservation of BB3394 in sequenced B. bronchiseptica genomes suggests the importance of this gene for bacteria normal physiology. Deletion of BB3394 abolished resistance to naive serum as described for other LPS mutants. When purified LPS was analyzed, differences in the LPS core structure were found. Particularly, a GalNA branched sugar substitution in the core was absent in the LPS obtained from BB3394 deletion mutant. Absence of GalNA in core LPS alters immune response in vivo but is able to induce protective response against B. bronchiseptica infection.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2016.12.049DOI Listing

Publication Analysis

Top Keywords

immune response
12
lps
9
bordetella bronchiseptica
8
sugar substitution
8
described lps
8
bronchiseptica
5
modifications bordetella
4
core
4
bronchiseptica core
4
core lipopolysaccharide
4

Similar Publications

The Role of Podocytes in Lupus Pathology.

Curr Rheumatol Rep

December 2024

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS-937, Boston, MA, 02215, USA.

Purpose Of Review: Kidney injury due to lupus nephritis (LN) is a severe and sometimes life-threatening sequela of systemic lupus erythematosus. Autoimmune injury to podocytes has been increasingly demonstrated to be a key driver of LN-related kidney injury because these cells play key roles in glomerular filtration barrier homeostasis. Irreparable podocyte injury impairs these processes and can lead to proteinuria, which is an indicator of poor prognosis in LN.

View Article and Find Full Text PDF

Background: Identifying patients with latent tuberculosis infection (LTBI) is challenging. This is particularly true amongst immunocompromised hosts, in whom the diagnostic accuracy of available tests is limited. The authors evaluated the impact of routine pretransplant review by a transplant infectious diseases (TID) physician on LTBI screening in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients.

View Article and Find Full Text PDF

Purpose Of Review: The canonical pathogenesis of spondyloarthritis (SpA) involves inflammation driven by HLA-B27, type 3 immunity, and gut microbial dysregulation. This review based on information presented at the SPARTAN meeting highlights studies on the pathogenesis of SpA from the past year, focusing on emerging mechanisms such as the roles of microbe-derived metabolites, microRNAs (miRNAs) and cytokines in plasma exosomes, specific T cell subsets, and neutrophils.

Recent Findings: The induction of arthritis in a preclinical model through microbiota-driven alterations in tryptophan catabolism provides new insights as to how intestinal dysbiosis may activate disease via the gut-joint axis.

View Article and Find Full Text PDF

Quantitative evaluation of the efficacy and safety of first-line systemic therapies for advanced hepatocellular carcinoma.

Eur J Clin Pharmacol

December 2024

Center for Pharmacometrics, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, No.1200 Cailun Road, Shanghai, 201203, China.

Objectives: This study aimed to quantitatively evaluate the efficacy and safety of first-line systemic therapies for treating advanced hepatocellular carcinoma (aHCC).

Methods: The study included clinical trials of first-line systemic therapies for aHCC since the approval of sorafenib in 2007. Hazard function models were used to describe changes in overall survival (OS) and progression-free survival (PFS) over time.

View Article and Find Full Text PDF

Chimeric Peptide-Engineered Polyprodrug Enhances Cytotoxic T Cell Response by Inducing Immunogenic Cell Death and Upregulating Major Histocompatibility Complex Class I.

ACS Nano

December 2024

The Fifth Affiliated Hospital, Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.

Tumor-specific cytotoxic T cell immunity is critically dependent on effective antigen presentation and sustained signal transduction. However, this immune response is frequently compromised by the inherently low immunogenicity of breast cancer and the deficiency in major histocompatibility complex class I (MHC-I) expression. Herein, a chimeric peptide-engineered stoichiometric polyprodrug (PDPP) is fabricated to potentiate the cytotoxic T cell response, characterized by a high drug loading capacity and precise stoichiometric drug ratio, of which the immunogenic cell death (ICD) inducer of protoporphyrin IX (PpIX) and the epigenetic drug of decitabine (DAC) are condensed into a polyprodrug called PpIX-DAC.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!