Table 6 Roles of differentially expressed oral metabolites in fungal-host interaction, Candida growth, and pathogenicity.

Sphingolipid

C17 sphinganine

Requires for stress response, apoptosis, inflammation, cell cycle regulation^32,33,34, biosynthetic fuel for immune-relevant signaling lipids³⁵; impairment causes insufficient clearance of Candida³⁶

Requires as a response to Candida overgrowth in fungal-host interactions³⁷, involves in the Candida infection-related signaling networks^38,39

Phytosphingosine

Ceramide

Requires for inflammatory response, phagocytosis and pathogen killing in innate immunity³⁵

Plays a role in in maintaining the properties of Candida plasma membrane and gaining resistance to antifungal agents⁴⁰

Amino acid

D-proline

Requires for cell growth and signaling⁴¹, stress protection⁴², energy production, and protein synthesis⁴³

Inactivation of proline catabolism diminishes the capacity of Candida to induce hyphal growth and evade macrophage killing⁴⁴

L-leucine

Essential for protein synthesis and structure^45,46

Disruption in leucine biosynthesis attenuates yeast virulence^47,48

L-valine

Essential for protein synthesis and structure⁴⁶

Disruption in biosynthesis may affect yeast virulence⁴⁸

Polyamine

Spermine

Essential nucleic acids (DNA and RNA) and protein synthesis; cellular metabolism & signaling⁴⁹; immunomodulation⁵⁰, dysregulation of the polyamine pathway leads to inflammation⁵¹

Virulence mechanisms of fungi^52,53

Spermidine

Glycerolipid

Monoacylglycerol (MG) (MG(0:0/18:0/0:0))

Essential for energy storage, signalling molecules modulating gene transcription and expression⁵⁴; post-transcriptional/translational modification of proteins, enzyme activities as co-activators⁵⁵

Positively influence long-term survival of yeast under certain stress conditions⁵⁶

Triacylglycerol (TG)

[TG(17:2(9Z,12Z)/22:2(13Z,16Z)/22:5(7Z,10Z,13Z,16Z,19Z))[iso6]]

Essential for energy generation⁵⁷

Secretion of hydrolytic enzymes, lipases, involves in proliferation, phenotypic switching, and cell–cell adhesion⁵⁸

Glycerophospholipid

Mannosyl inositol phosphorylceramide (MIPC)

(t18:0/18:0(2OH))

Components of fungal lipid rafts which contribute to morphogenesis⁵⁹

Essential for virulence mechanisms and Candida infectivity⁶⁰

Phosphoethanolamine (PE)

[PE(17:2(9Z,12Z)/22:6

(4Z,7Z,10Z,13Z,16Z,19Z)]

Constitutes phospholipid in the inner plasma membrane, essential for cellular processes⁶¹, lipid signalling and immune recognition⁶²

Essential for Candida infectivity^63,64

Phosphatidylglycerol (PG)

[PG(20:0/0:0)]

Precursor for the biosynthesis of cardiolipin, signalling molecule for various cellular functions⁶⁵

Candida growth on nonfermentable carbon sources^66,67; its absence suggests Candida overgrowth⁶⁸

Phosphatidylinositol (PI)

[PI(12:0/12:0)]

Essential for cell physiology, cell-signaling pathways, actin cytoskeletal remodeling and membrane dynamics^69,70

Regulates polarized hyphal growth which is important for Candida infection and virulence⁷¹

Phosphatidylserine (PS)

[PS(P-20:0/17:1(9Z))]

Requires for phagocytic recognition and removal⁷²

Requires for PE synthesis, reduces Candida virulence^73,74