Synthesis and immunological evaluation of Pel and Psl glycoconjugate vaccine candidates against Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a Gram-negative opportunistic pathogen that presents a significant challenge in both clinical and environmental settings. It is an antimicrobial-resistant bacterium responsible for severe infections and is classified among the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens, which are major contributors to nosocomial infections and antibiotic resistance. These pathogens are particularly concerning due to their ability to evade the effects of many antibiotics, making infections difficult to treat. P. aeruginosa is commonly implicated in a wide range of infections, including pneumonia, urinary tract infections, bloodstream infections, and burn wound infections. Moreover, it poses a severe threat to patients with cystic fibrosis, where it can establish persistent lung infections that are difficult to eliminate due to its biofilm-forming ability.

Biofilm formation is a critical virulence factor of P. aeruginosa, significantly contributing to its persistence in both clinical and environmental settings. These biofilms are three-dimensional structures composed of a dense extracellular matrix of extracellular polymeric substances (EPS), which primarily consist of polysaccharides, proteins, lipids, and extracellular DNA (eDNA), forming a protective matrix around the bacterial cells. The EPS matrix provides structural integrity to the biofilm, helps in water retention, and facilitates the attachment of bacteria to surfaces, which is essential for biofilm formation. Three distinct exopolysaccharides, alginate, Pel and Psl, are crucial for the development of P. aeruginosa biofilms, playing essential roles in promoting bacterial adhesion, maintaining structural integrity, and enhancing resistance to environmental stresses, including host immune defenses and antimicrobial agents. Psl and Pel are crucial for the early stages of P. aeruginosa biofilm formation, aiding in surface attachment, bacterial aggregation, matrix support, and antibiotic resistance. In contrast, alginate, primarily produced by mucoid P. aeruginosa, contributes to the structure of the mature biofilm, providing additional support and enhancing resistance to environmental stresses and antibiotics.