The Anti-Infectious Role of Sphingosine in Microbial Diseases

Abstract

Sphingolipids are important structural membrane components and, together with cholesterol, are often organized in lipid rafts, where they act as signaling molecules in many cellular functions. They play crucial roles in regulating pathobiological processes, such as cancer, inflammation, and infectious diseases. The bioactive metabolites ceramide, sphingosine-1-phosphate, and sphingosine have been shown to be involved in the pathogenesis of several microbes. In contrast to ceramide, which often promotes bacterial and viral infections (for instance, by mediating adhesion and internalization), sphingosine, which is released from ceramide by the activity of ceramidases, kills many bacterial, viral, and fungal pathogens. In particular, sphingosine is an important natural component of the defense against bacterial pathogens in the respiratory tract. Pathologically reduced sphingosine levels in cystic fibrosis airway epithelial cells are normalized by inhalation of sphingosine, and coating plastic implants with sphingosine prevents bacterial infections. Pretreatment of cells with exogenous sphingosine also prevents the viral spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from interacting with host cell receptors and inhibits the propagation of herpes simplex virus type 1 (HSV-1) in macrophages. Recent examinations reveal that the bactericidal effect of sphingosine might be due to bacterial membrane permeabilization and the subsequent death of the bacteria.

New holistic approach for the management of biofilm‐associated infections by myco‐metabolites

“…Sphingosine, present in filamentous fungi, is profoundly effective against planktonic and disrupted biofilms [16]. The bactericidal effect of sphingosine Staphylococcus epidermidis biofilms formed on different implant materials [18]. Sphinganine-like backbone is found to be present in a number of fungal toxins, produced by fungus Alternaria alternata f. sp.…”

CFTR Protein: Not Just a Chloride Channel?

“…Cell interaction, adhesion, proliferation, migration, and death are in part regulated by sphingolipids. In addition to being part of the plasma membrane, ceramide, sphingosine, and sphingosine-1-phosphate (S1P), which are the key molecules of sphingolipid signaling, are involved in cell processes and pathological processes, such as inflammation, as well [ 80 ]. As mentioned above, sphingolipids play an important role in the pathophysiology of CF.…”

“…In CF, sphingosine concentrations are decreased in airway epithelial cells due to the repressed acid ceramidase activity, which contributes to the high infection susceptibility to CF pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa . This bactericidal activity of sphingosine itself is also pH dependent and is profoundly reduced at alkaline pH [ 80 ]. Sphingosine is phosphorylated into S1P by sphingosine kinases.…”

Sphingolipids: Effectors and Achilles Heals in Viral Infections?

“…Interaction of the viral spike protein with its receptor-binding domain of ACE2 was found to be prevented upon exogenous supply of sphingosine, which directly associated with this receptor [ 91 ]. Thus, sphingosine, known for its bacteriocidal activities in the respiratory tract (recently reviewed in [ 92 , 93 ]), might also exert antiviral activities at the level of entry in this particular compartment ( Figure 6 ).…”