SYNTHESIS OF ACINETOBACTER BAUMANNII LAC-4 POLYSACCHARIDE FRAGMENTS

Acinetobacter baumannii (Ab) is a highly adaptable opportunistic pathogen known for its multidrug resistance and increasing prevalence in nosocomial and community-acquired infections, including pneumonia and severe urinary tract infections. Its ability to persist on abiotic surfaces for extended period of time facilitates its survival in hospital environments, making it a serious global health threat1,2. Hence, investigating its virulence factors is crucial for developing novel therapeutics and vaccines. In particular LAC-4 was identified as hypervirulent strain in a mouse model of intranasal infection in comparison to other clinical isolates and laboratory strains of Ab. Importantly, the LAC-4 strain exhibits high serum resistance and reliably reproduces the most relevant features of human pulmonary Ab infection, including significant extrapulmonary dissemination and bacteremia3. LAC-4 polysaccharide is composed of trisaccharide repeating units (1, Figure 1) containing N-acetylα-D-glucosamine (a), N-acetyl-α-L-fucosamine (b) and α-8-epi-legionaminic acid (c). Synthetic fragments of Ab bacterial polysaccharides can be valuable tools to understand how the polysaccharide interacts with receptors of the immune system and to be used for antigen mapping studies, with the aim of investigating the possible development of semisynthetic glycoconjugate vaccines capable of conferring protection against Ab infections. Hence, our group embarked on the synthesis of LAC-4 polysaccharide fragments, including the trisaccharide repeating unit and longer oligomers. As a first step of this endeavour, in this communication we will describe the design and synthesis of 8epiLegionaminic acid building block, and its incorporation into the full trisaccharide repeating unit of LAC-4 polysaccharide. The synthetic glycans will be chemically conjugated to different carriers (immunogenic proteins and nanoparticles) for immunoevaluation.