Synthetic Pseudaminic-Acid-Based Antibacterial Vaccine Confers Effective Protection against Acinetobacter baumannii Infection

Abstract

Acinetobacter baumannii exhibits resistance to most first-line antibiotics; thus, development of new antibacterial agents is urgently required. Pseudaminic acid exists as the surface glycan of A. baumannii . In this study, we chemically synthesized pseudaminic acid, conjugated it to carrier protein CRM197 using the OPA ( ortho -phthalaldehyde) chemistry, and obtained three Pse–CRM197 conjugates with different Pse loadings. These Pse–CRM197 conjugates were found to stimulate high immune responses in mice, which protected the vaccinated mice from infections caused by Pse-producing A. baumannii . Our data indicate that chemically synthesized Pse–CRM197 conjugates can be developed into vaccines against Pse-bearing pathogens, thus offering a feasible alternative for the control of clinical infections caused by multidrug-resistant (MDR) A. baumannii , for which current treatment options are extremely limited.

Immune Response to Conjugates of Fragments of the Type K9 Capsular Polysaccharide of Acinetobacter baumannii with Carrier Proteins

“…The carbohydrate components of the existing conjugate vaccines against A. baumannii are pseudaminic acid for the protection of mice against infections by pseudaminic acid-producing strains ( 43 ) and poly-N-acetyl-β-(1-6)-glucosamine (PNAG), which is expressed by a wide range of bacterial pathogens ( 44 ). Outer membrane vesicles decorated with PNAG possess a high protective potential against bacterial pathogens displaying PNAG on their cell surfaces ( 45 ).…”

Genetic glyco-profiling and rewiring of insulated flagellin glycosylation pathways

“…Such long-term goals are achievable, but ideally facilitated by the discovery and dissection of the determinants underpinning the GT specificities, including acceptor and donor. In addition to illuminating the molecular mechanism of FlmG fGTs, our work also opens the door towards biotechnological engineering of flagellin-based bio-glycoconjugates using Pse or Leg for example as simple vaccine [43][44][45] that could serve to combat Pse/Leg in infections by prior immunization not only for A. baumannii strains or other pathogens that decorate surfaces with Pse, but, importantly, also for those that contain Leg, including most clinical A. baumannii isolates [12,34,46].…”

“…Pse and Leg derivatives synthesized in vitro can be added exogenously in metabolic labeling experiments to be incorporated into bacterial surface structures [10, 11]. Moreover, Pse and Leg are attractive vaccine targets as shown by the recent report that mice immunized with Pse chemically conjugated to a carrier protein were protected against the Pse-containing pathogenic Acinetobacter baumannii strain Ab-00.191 [12].…”

Biological Evaluation of Azide Derivative as Antibacterial and Anticancer Agents

“…The Gram-negative bacillus bacterium A. baumannii is one of the most challenging resistant organisms to eradicate (Wei et al, 2021). The most well-known feature of the species, A. baumannii, is its capacity to infect immunocompromised humans.…”