Promoter-Controlled Synthesis and Antigenic Evaluation of Mannuronic Acid Alginate Glycans of <i>Pseudomonas aeruginosa</i>

Zhang, Liangliang; Zhang, Yiyue; Hua, Qingting; Xu, Tong; Liu, Junru; Zhu, Yirong; Yang, You

doi:10.1021/acs.orglett.2c03439

Cited by 15 publications

(9 citation statements)

References 33 publications

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“…To this end, the mannuronic acid tetrasaccharide 1 obtained by the bimodal glycosylation of glycosyl ynenoates has been identified as the optimal antigenic epitope for recognition with the sera antibodies from mice immunized with inactivated P. aeruginosa from six synthetic mannuronic acid alginate glycans ranging from the monomer to the 24-mer (Figure 1b). 24,25 We aimed to use the simple and highly conserved synthetic mannuronic acid tetrasaccharide to develop a broadly protective semisynthetic glycoconjugate vaccine candidate against antibiotic-resistant P. aeruginosa, overcoming the heterogeneity and potential contamination associated with the isolated glycan antigens.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa

Zhang,

Wang,

Liang

et al. 2024

ACS Cent. Sci.

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Pseudomonas aeruginosa is one of the leading causes of nosocomial infections and has become increasingly resistant to multiple antibiotics. However, development of novel classes of antibacterial agents against multidrug-resistant P. aeruginosa is extremely difficult. Herein we develop a semisynthetic oligomannuronic acid-based glycoconjugate vaccine that confers broad protection against infections of both mucoid and nonmucoid strains of P. aeruginosa. The well-defined glycoconjugate vaccine formulated with Freund's adjuvant (FA) employing a highly conserved antigen elicited a strong and specific immune response and protected mice against both mucoid and nonmucoid strains of P. aeruginosa. The resulting antibodies recognized different strains of P. aeruginosa and mediated the opsonic killing of the bacteria at varied levels depending on the amount of alginate expressed on the surface of the strains. Vaccination with the glycoconjugate vaccine plus FA significantly promoted the pulmonary and blood clearance of the mucoid PAC1 strain of P. aeruginosa and considerably improved the survival rates of mice against the nonmucoid PAO1 strain of P. aeruginosa. Thus, the semisynthetic glycoconjugate is a promising vaccine that may provide broad protection against both types of P. aeruginosa.

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Section: ■ Results and Discussionmentioning

confidence: 99%

A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa

Zhang,

Wang,

Liang

et al. 2024

ACS Cent. Sci.

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“…As alginate of P. aeruginosa mediates pathogenesis in host cells, one main target of efforts is to design therapeutic vaccines. Immunity against P. aeruginosa in mice has also been induced by using mannuronic acid tetrasaccharide, as antigen epitope for vaccine development [ 127 ].…”

Section: Main Textmentioning

confidence: 99%

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

et al. 2023

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The opportunistic human pathogen Pseudomonas aeruginosa is the causal agent of a wide variety of infections. This non-fermentative Gram-negative bacillus can colonize zones where the skin barrier is weakened, such as wounds or burns. It also causes infections of the urinary tract, respiratory system or bloodstream. P. aeruginosa infections are common in hospitalized patients for which multidrug-resistant, respectively extensively drug-resistant isolates can be a strong contributor to a high rate of in-hospital mortality. Moreover, chronic respiratory system infections of cystic fibrosis patients are especially concerning, since very tedious to treat. P. aeruginosa exploits diverse cell-associated and secreted virulence factors, which play essential roles in its pathogenesis. Those factors encompass carbohydrate-binding proteins, quorum sensing that monitor the production of extracellular products, genes conferring extensive drug resistance, and a secretion system to deliver effectors to kill competitors or subvert host essential functions. In this article, we highlight recent advances in the understanding of P. aeruginosa pathogenicity and virulence as well as efforts for the identification of new drug targets and the development of new therapeutic strategies against P. aeruginosa infections. These recent advances provide innovative and promising strategies to circumvent infection caused by this important human pathogen.

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“…3 In subsequent studies with Codée, the construction of the analogous oligomer containing L-GulA 4 and a mixed sequence fragment 5 were both achieved. Excellent reviews of alginate synthesis are provided by Clausen, 6 Cai 7 and Codée; 8 all precede the very recent advance of Yang 9 who has https://doi.org/10.26434/chemrxiv-2024-sns6w ORCID: https://orcid.org/0000-0003-3306-2550 Content not peer-reviewed by ChemRxiv. License: CC BY-NC-ND 4.0 Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Access to L-Guluronic Acid via Fluorine-Directed C-5 Epimerization

See,

Wimmer,

Zhang

et al. 2024

Preprint

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L-Guluronic acid is integral to the structures of alginates and to the pathogenesis of Pseudomonas aeruginosa. The exploitation of this hexose in both existing and new contexts is, however, limited by its prohibitively high commercial cost. We report on a short and efficient synthetic route to an L-GulA building block from a simple D-mannose thioglycoside. In this synthesis, the fluorine-directing effect is exploited to achieve a stereoselective C-5 epimerization. DFT calculations illuminate the substituent effects which operate to confer this selectivity.

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Promoter-Controlled Synthesis and Antigenic Evaluation of Mannuronic Acid Alginate Glycans of Pseudomonas aeruginosa

Cited by 15 publications

References 33 publications

A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa

A Semisynthetic Oligomannuronic Acid-Based Glycoconjugate Vaccine against Pseudomonas aeruginosa

Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections

Synthetic Access to L-Guluronic Acid via Fluorine-Directed C-5 Epimerization

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