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Published on: October 13, 2015
Yersinia enterocolitica O:3 Outer Membrane Vesicles as a Platform for Complement Activation
Cédric Battaglino1,2, Iryna Bodnaruk3, Paula Czyszczoń4
1Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Abstract:
Lipopolysaccharide (LPS) is the major component of the outer membrane vesicles (OMVs) of Gram-negative bacteria. We hypothesized that OMVs-induced complement activation contributes to the development of systemic inflammatory response syndrome (SIRS). Yersinia enterocolitica O:3 (YeO3) variants synthesizing LPS of various chemotypes (S, Ra, Rd1, Re) were used as model microorganisms. OMVs activated complement more potently than parental bacteria or homologous LPS, independently of chemotype. A high molecular weight polysaccharide fraction, distinct from LPS, was recognized by serum mannose-binding lectin (MBL). In vivo experiments demonstrated that complement depletion weakened the hallmarks of OMVs-induced SIRS in mice. LPS chemotype affected the biodistribution of OMVs and long O-specific polysaccharide protected them from clearance. Chemotype influenced OMVs secretion with their highest release by bacteria with LPS reduced to the inner core and lipid A (Rd1). The shift from environmental to host's temperature stimulated secretion of smaller OMVs, with less-toxic, tetra-acyl lipid A. Our data are consistent with a contribution of OMVs to Yersinia pathogenicity through complement activation. Their potency as complex virulence factor is influenced by size, length of oligo-/polysaccharide chain, and lipid A form. This study comprehensively characterizes OMV-complement interactions in YeO3, extending the knowledge of mechanisms previously established for other Gram-negative bacteria.
Insights
Outer membrane vesicles (OMVs) from Gram-negative bacteria, like Yersinia enterocolitica, activate complement and contribute to systemic inflammatory response syndrome (SIRS). OMVs are potent virulence factors influenced by their composition and size.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Lipopolysaccharide (LPS) is a key component of Gram-negative bacterial outer membrane vesicles (OMVs).
- OMVs are implicated in bacterial pathogenesis and can trigger inflammatory responses.
Purpose of the Study:
- To investigate the role of OMVs from Yersinia enterocolitica (YeO3) in complement activation and systemic inflammatory response syndrome (SIRS).
- To determine how LPS chemotype and OMV characteristics influence virulence and host response.
Main Methods:
- Utilized YeO3 variants with different LPS chemotypes (S, Ra, Rd1, Re) to produce OMVs.
- Assessed complement activation by OMVs, LPS, and bacteria.
- Conducted in vivo experiments in mice with complement depletion.
- Analyzed OMV biodistribution, clearance, and secretion influenced by LPS structure and temperature.
Main Results:
- OMVs potently activated complement independently of LPS chemotype.
- A distinct polysaccharide fraction bound mannose-binding lectin (MBL).
- Complement depletion reduced SIRS severity in mice.
- LPS O-specific polysaccharide length influenced OMV biodistribution and clearance.
- Bacteria with truncated LPS (Rd1) secreted the most OMVs.
- Temperature shift increased secretion of smaller OMVs with less toxic lipid A.
Conclusions:
- OMVs contribute to Yersinia pathogenicity via complement activation.
- OMV potency as virulence factors depends on size, polysaccharide chain length, and lipid A structure.
- This study elucidates OMV-complement interactions in YeO3, expanding knowledge on Gram-negative bacterial virulence mechanisms.
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