Found 2 publications. Displayed publications from 1 to 2
Expand all publications       Show all as text (SweetDB notation)
1. (Article ID: 5162)
 
Jacobson AN, Choudhury BP, Fischbach MA
The Biosynthesis of Lipooligosaccharide from Bacteroides thetaiotaomicron
mBio 9(2) (2018) e02289-17
 

Lipopolysaccharide (LPS), a cell-associated glycolipid that makes up the outer leaflet of the outer membrane of Gram-negative bacteria, is a canonical mediator of microbe-host interactions. The most prevalent Gram-negative gut bacterial taxon, Bacteroides, makes up around 50% of the cells in a typical Western gut; these cells harbor similar to 300 mg of LPS, making it one of the highest-abundance molecules in the intestine. As a starting point for understanding the biological function of Bacteroides LPS, we have identified genes in Bacteroides thetaiotaomicron VPI 5482 involved in the biosynthesis of its lipid A core and glycan, generated mutants that elaborate altered forms of LPS, and used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry to interrogate the molecular features of these variants. We demonstrate, inter alia, that the glycan does not appear to have a repeating unit, and so this strain produces lipooligosaccharide (LOS) rather than LPS. This result contrasts with Bacteroides vulgatus ATCC 8482, which by SDS-PAGE analysis appears to produce LPS with a repeating unit. Additionally, our identification of the B. thetaiotaomicron LOS oligosaccharide gene cluster allowed us to identify similar clusters in other Bacteroides species. Our work lays the foundation for developing a structure-function relationship for Bacteroides LPS/LOS in the context of host colonization. IMPORTANCE Much is known about the bacterial species and genes that make up the human microbiome, but remarkably little is known about the molecular mechanisms through which the microbiota influences host biology. A well-known mechanism by which bacteria influence the host centers around lipopolysaccharide (LPS), a component of the Gram-negative bacterial outer membrane. Pathogen-derived LPS is a potent ligand for host receptor Toll-like receptor 4, which plays an important role in sensing bacteria as part of the innate immune response. Puzzlingly, the most common genus of human gut bacteria, Bacteroides, produces LPS but does not elicit a potent proinflammatory response. Previous work showing that Bacteroides LPS differs structurally from pathogen-derived LPS suggested the outlines of an explanation. Here, we take the next step, elucidating the biosynthetic pathway for Bacteroides LPS and generating mutants in the process that will be of great use in understanding how this molecule modulates the host immune response.

Lipopolysaccharide, biosynthesis, Lipooligosaccharide, Bacteroides, microbiome

The publication contains the following compound(s):
 

Expand this publication
2. (Article ID: 6294)
 
Pither MD, Illiano A, Pagliuca C, Jacobson A, Mantova G, Stornaiuolo A, Colicchio R, Vitiello M, Pinto G, Silipo A, Fischbach MA, Salvatore P, Amoresano A, Molinaro A, Di Lorenzo F
Bacteroides thetaiotaomicron rough-type lipopolysaccharide: The chemical structure and the immunological activity
Carbohydrate Polymers 297 (2022) 120040
 

Bacteroides thetaiotaomicron is one of the most extensively studied symbionts of the human gut. Despite its widespread distribution among human populations, still very little is known about the role of its cell envelope in the crosstalk with the immune system. Due to the extraordinary characteristic of B. thetaiotaomicron to express multiple capsular polysaccharides on its surface, research activities focused on defining how these polymers affect immune responses. This resulted in the drawback of neglecting another immunostimulatory cell surface glycoconjugate, the lipopolysaccharide (LPS). By taking advantage of an acapsular mutant of B. thetaiotaomicron, here we describe the characterization of the structure of the rough-type LPS produced by this gut mutualist. This was made up of a mono-phosphorylated and hypoacylated lipid A and of a highly charged core oligosaccharide. In vitro studies revealed a weak ability to engage the MD-2/TLR4 pathway, while it was able to promote TLR2-mediated response.

lipid A, lipopolysaccharide (LPS), gut microbiota, Bacteroides thetaiotaomicron, commensal LPS, structure to function

The publication contains the following compound(s):
 

Expand this publication

Resort publications by:

New query Export IDs Home Help

Execution: <1 sec