Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria

Abstract

Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C6 and long-chain C16-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C6-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C6-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C6-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.

Isolation and Characterization of Plant Growth-Promoting Endophytic Bacteria Paenibacillus polymyxa SK1 from Lilium lancifolium

“…Sphinganine belonging to sphingosines and sphingolipids was identified in the isolated strain SK1. Previous studies have demonstrated that several sphingoid bases and fatty acids act as antimicrobial agents [54,55]. Tetrodotoxin (TTX) is a strong marine toxin which is a powerful sodium channel inhibitor.…”

Sphingosine-coating of plastic surfaces prevents ventilator-associated pneumonia

“…At present, it is unknown how sphingosine kills bacteria. It is known that micellar sphingosine kills many pathogens including E. coli , P. aeruginosa , S. aureus , A. baumannii , Moraxella catarrhalis , Haemophilus influenzae , Burkholderia cepacia , Neisseria meningitides , and Neisseria gonorrhoeae [10–15, 25]. It is possible that sphingosine simply kills pathogens by its biophysical properties, which would also suggest that sphingosine’s antimicrobial mechanism is not prone to development of bacterial resistance.…”

Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro

“…The molecular mechanism of sphingosine's bactericidal effect has not yet been fully resolved in detail. It is known that micellar sphingosine kills many pathogens including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Moraxella catarrhalis, Haemophilus influenzae, Burkholderia cepacia, Neisseria meningitides, and Neisseria gonorrhoeae [9,[29][30][31][32][33][34]. It is possible that sphingosine simply kills pathogens by its biophysical properties, which would also suggest that sphingosine's antimicrobial mechanism is not prone to the development of bacterial resistance.…”