Intracellular Staphylococcus aureus Elicits the Production of Host Very Long-Chain Saturated Fatty Acids with Antimicrobial Activity

Abstract

As a facultative intracellular pathogen, Staphylococcus aureus is able to invade and proliferate within many types of mammalian cells. Intracellular bacterial replication relies on host nutrient supplies and, therefore, cell metabolism is closely bound to intracellular infection. Here, we investigated how S. aureus invasion affects the host membrane-bound fatty acids. We quantified the relative levels of fatty acids and their labelling pattern after intracellular infection by gas chromatography-mass spectrometry (GC-MS). Interestingly, we observed that the levels of three host fatty acids—docosanoic, eicosanoic and palmitic acids—were significantly increased in response to intracellular S. aureus infection. Accordingly, labelling carbon distribution was also affected in infected cells, in comparison to the uninfected control. In addition, treatment of HeLa cells with these three fatty acids showed a cytoprotective role by directly reducing S. aureus growth.

Increased resistance of a methicillin-resistant Staphylococcus aureus Δagr mutant with modified control in fatty acid metabolism

“…Additionally, innate immune system in epithelial cell and in abscesses Fig. 6 Semi-quantitative RT-PCR of mecA and the fatty acid synthetic operon take advantage of long chain free fatty acids such as linoleic acid [C18:2 (n-6,9)], oleic acid [C18:1 (n-9)] and palmitoleic acid [C16:1 (n-7)], which are unsaturated fatty acids and saturated palmitic acid (C16:0) and stearic acid (C18:0) (Bravo-Santano et al 2019b;Kenny et al 2009). These major long chain fatty acids are considered bactericidal or bacteriostatic depending on their structural characteristics and they induce stress response of S.aureus.…”

“…However, hexadecenoic acid (C16:0), octadecanoic acid (C18:0) and eicosanoic acid (C20:0) could reduce biofilm formation in this study. This might be from the different culture condition including medium, bacterial strain and dose-dependent supplementation of fatty acid (Bravo-Santano et al 2019a;Lade et al 2019;Yoon et al 2018). As a conclusion, this phenomenon might explain how the Δagr mutant strain retained a lower level of fatty acid in the supernatant, since maintaining higher levels of fatty acids would interfere with biofilm formation and increase the instability of the cytoplasmic membrane leading to higher antibiotic susceptibility.…”

Increased resistance of a methicillin-resistant Staphylococcus aureus Δagr mutant with modified control in fatty acid metabolism

“…However, hexadecenoic acid (C16:0), octadecanoic acid (C18:0) and eicosanoic acid (C20:0) could reduce biofilm formation in this study. This might be from the different culture condition including medium, bacterial strain and dose-dependent supplementation of fatty acid (Bravo-Santano et al 2019a;Lade et al 2019;Yoon et al 2018). As a conclusion, this phenomenon might explain how the Δagr mutant strain retained a lower level of fatty acid in the supernatant, since maintaining higher levels of fatty acids would interfere with biofilm formation and increase the instability of the cytoplasmic membrane leading to higher antibiotic susceptibility.…”

Bacteriophages Promote Metabolic Changes in Bacteria Biofilm

“…It has been reported that C20:0 does not show a significant decrease in biofilm formation, especially at low concentration [33]. However, inhibition has been reported to be dose-dependent [34][35][36].…”