Pushing the Boundaries of Structural Heterogeneity with the Lipid A of Marine Bacteria Cellulophaga

• Published in: Chembiochem : a European journal of chemical biology Vol. 24; no. 10; pp. e202300183 - n/a
• Main Authors: Cirella, Roberta, Pagliuca, Chiara, Pither, Molly Dorothy, Scaglione, Elena, Nedashkovskaya, Olga I., Chernikov, Oleg V., Hua, Kuo‐Feng, Colicchio, Roberta, Vitiello, Mariateresa, Kokoulin, Maxim S., Silipo, Alba, Salvatore, Paola, Molinaro, Antonio, Di Lorenzo, Flaviana
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 16.05.2023
• Subjects: Adjuvants; Bacteria; Cellulophaga; Disaccharides; Flavobacteriaceae; Gammaproteobacteria; Glucosamine; Heterogeneity; Lipid A; Lipid A - chemistry; Lipids; Lipopolysaccharide (LPS); Lipopolysaccharides; Lipopolysaccharides - chemistry; MALDI-TOF mass spectrometry; Mannose; Marine bacteria; Sepsis; TLR4 protein; Toll-Like Receptor 4; Toll-like receptors; MALDI-TOF mass spectrometry; Lipid A; Cellulophaga; Lipopolysaccharide (LPS); Marine bacteria
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202300183

Marine bacteria, which are often described as chemical gold, are considered an exceptional source of new therapeutics. Considerable research interest has been given to lipopolysaccharides (LPSs), the main components of the Gram‐negative outer membrane. LPS and its lipid A portion from marine bacteria are known to exhibit a tricky chemistry that has been often associated with intriguing properties such as behaving as immune adjuvants or anti‐sepsis molecules. In this scenario, we report the structural determination of the lipid A from three marine bacteria within the Cellulophaga genus, which showed to produce an extremely heterogenous blend of tetra‐ to hexa‐acylated lipid A species, mostly carrying one phosphate and one D‐mannose on the glucosamine disaccharide backbone. The ability of the three LPSs in activating TLR4 signaling revealed a weaker immunopotential by C. baltica NNO 15840T and C. tyrosinoxydans EM41T, while C. algicola ACAM 630T behaved as a more potent TLR4 activator. Lipopolysaccharide and its lipid A from marine bacteria are a chemical gold for the development of new adjuvants and immune therapeutics. Here we defined the structure of three marine Cellulophaga species and the TLR4 activation potential of their lipopolysaccharide. An extreme structural heterogeneity has been disclosed that resulted in a weak TLR4 immunostimulatory capacity for two of the species analyzed.