Interaction of Mannose-Binding Lectin With Lipopolysaccharide Outer Core Region and Its Biological Consequences

Abstract

Lipopolysaccharide (LPS, endotoxin), the main surface antigen and virulence factor of Gram-negative bacteria, is composed of lipid A, core oligosaccharide, and O-specific polysaccharide (O-PS) regions. Each LPS region is capable of complement activation. We have demonstrated that LPS of Hafnia alvei, an opportunistic human pathogen, reacts strongly with human and murine mannose-binding lectins (MBLs). Moreover, MBL–LPS interactions were detected for the majority of other Gram-negative species investigated. H. alvei was used as a model pathogen to investigate the biological consequences of these interactions. The core oligosaccharide region of H. alvei LPS was identified as the main target for human and murine MBL, especially l-glycero-d-manno-heptose (Hep) and N-acetyl-d-glucosamine (GlcNAc) residues within the outer core region. MBL-binding motifs of LPS are accessible to MBL on the surface of bacterial cells and LPS aggregates. Generally, the accessibility of outer core structures for interaction with MBL is highest during the lag phase of bacterial growth. The LPS core oligosaccharide–MBL interactions led to complement activation and also induced an anaphylactoid shock in mice. Unlike Klebsiella pneumoniae O3 LPS, robust lectin pathway activation of H. alvei LPS in vivo was mainly the result of outer core recognition by MBL; involvement of the O-PS is not necessary for anaphylactoid shock induction. Our results contribute to a better understanding of MBL–LPS interaction and may support development of therapeutic strategies against sepsis based on complement inhibition.

Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment

“…Among them there were Enterococcus faecalis and Proteus isolates. These finding are in agreement with previous reports by Geiss-Liebisch et al (2012) 2 and Man-Kupisinska et al (2018) 3 . Geiss-Liebisch demonstrated that wall teichoic acids and rhamnopolysaccharide of E. faecalis prevent peptidoglycan from MBL binding.…”

The Role of Pseudomonas aeruginosa Lipopolysaccharide in Bacterial Pathogenesis and Physiology

“…The complement cascade can be activated by the classical mannose-binding lectin, as well as alternative pathways [59]. Lipid A, core, and O antigen activate one or more of these pathways but bacteria expressing long O antigen chains are usually more resistant to serum than their O antigen-deficient isogenic mutants [60][61][62][63][64][65][66]. However, specific chain lengths of O antigen have been shown to be important in conferring resistance [67][68][69][70][71][72][73].…”

Outer membrane vesicle-mediated serum protection inAggregatibacter actinomycetemcomitans

“…Moreover, LPS derived from a number of Gram-negative bacteria can block the serum bactericidal activity [33,57], and interact with the classical complement factor C1q, in an antibodyindependent fashion, to activate the classical pathway [58,59]. LPS is also a well-recognized alternative complement activator [60], and furthermore, it can trigger the MBL pathway [61].…”