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Chemical Synthesis of Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii Capsular
Amar Kumar Mishra1, Emelie E Reuber2,3, Diksha Rai1
1Department of Chemistry, Indian Institution of Technology Bombay, Powai, Mumbai, India.
Abstract:
Pseudomonas aeruginosa and Staphylococcus aureus are listed by the World Health Organization as high-priority multidrug-resistant (MDR) pathogens, whereas Acinetobacter baumannii is classified as the critical-priority group. These bacteria cause life-threatening infections such as severe bloodstream, nosocomial, urinary tract, and soft-tissue infections. Their cell surfaces display complex and structurally distinct glycans absent in host cells, making them targets for glycoconjugate vaccine and diagnostic research. In this study, we report the chemical synthesis of mono- and oligosaccharide fragments derived from three ESKAPE pathogens, P. aeruginosa O11, S. aureus (CP5, CP8, and strain M), and A. baumannii (S34 and O5), as well as Plesiomonas shigelloides O1. Glycan microarray screening revealed three epitopes exhibiting strong cross-reactive immunogenicity against P. aeruginosa, S. aureus, and A. baumannii, demonstrating that a trisaccharide represents the minimal epitope required to elicit cross-protective immune responses. The key features of P. aeruginosa O11 trisaccharide synthesis involve efficient assembly of a 1,2-cis-linked l-FucNAc-linker motif, followed by regioselective glycosylation at O3 and subsequently at O2 of the d-Glc-l-FucNAc-linker disaccharide. The same strategy was applied for assembling its tetrasaccharide fragment. Additionally, β-mannosylation and 1,2-cis-d-FucNAc linkage formations were optimized for the S. aureus CP8 fragment, establishing a versatile route toward bacterial glycans relevant for vaccine and diagnostic development.
Insights
Scientists chemically synthesized bacterial glycan fragments from high-priority pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. A trisaccharide epitope was identified as the minimal structure for cross-protective immune responses against these difficult-to-treat infections.
Area of Science:
- Carbohydrate Chemistry
- Vaccinology
- Microbiology
Background:
- Multidrug-resistant (MDR) pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii, pose significant global health threats.
- These bacteria possess unique cell surface glycans, absent in humans, making them attractive targets for vaccine and diagnostic development.
- The World Health Organization highlights these ESKAPE pathogens as high and critical priority due to the life-threatening infections they cause.
Purpose of the Study:
- To chemically synthesize mono- and oligosaccharide fragments from key ESKAPE pathogens and Plesiomonas shigelloides.
- To identify conserved glycan epitopes with cross-reactive immunogenicity for potential vaccine development.
- To establish efficient synthetic routes for bacterial glycans relevant to combating MDR infections.
Main Methods:
- Chemical synthesis of mono- and oligosaccharide fragments from P. aeruginosa O11, S. aureus (CP5, CP8, strain M), A. baumannii (S34, O5), and P. shigelloides O1.
- Glycan microarray screening to identify immunogenic epitopes.
- Optimization of specific glycosylation reactions, including 1,2-cis-linked l-FucNAc and β-mannosylation.
Main Results:
- Identification of three cross-reactive epitopes with immunogenicity against P. aeruginosa, S. aureus, and A. baumannii.
- Demonstration that a trisaccharide represents the minimal epitope for eliciting cross-protective immune responses.
- Successful synthesis strategies for P. aeruginosa O11 trisaccharide and tetrasaccharide fragments, and S. aureus CP8 fragment.
Conclusions:
- A trisaccharide epitope is sufficient for inducing cross-protective immunity against a range of priority bacterial pathogens.
- The developed chemical synthesis methods provide versatile routes for generating bacterial glycans for vaccine and diagnostic applications.
- This research advances the development of novel strategies to combat infections caused by multidrug-resistant bacteria.
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