Interaction of triclosan with eukaryotic membrane lipids

Lygre, Henning; Moe, Grete; Skålevik, Rita; Holmsen, Holm

doi:10.1034/j.1600-0722.2003.00034.x

Cited by 34 publications

(29 citation statements)

References 15 publications

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“…A more likely possibility is that the fatty acid remodeling and myristate exchange pathways are being nonspecifically inhibited by triclosan, perhaps by perturbation of the membrane structure. Triclosan, being very hydrophobic, has been shown to incorporate into bacterial and eukaryotic membranes and to alter the physicochemical properties of artificial lipid bilayers and liposomes in concentrations comparable to those used in this study (18,24,32) and likely affects other essential pathways in the membranes of both bloodstream and procyclic trypanosomes. However, triclosan-induced changes in the organellar membrane would have to be subtle, as an examination of BiP (an ER luminal protein) and lipoamide dehydrogenase (a mitochondrial matrix protein) immunofluorescence in cells treated with triclosan (5 to 20 M for 48 h or 100 M for 5.25 h) showed no change in ER or mitochondrial morphology, respectively (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Multiple Triclosan Targets in Trypanosoma brucei

2004

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Trypanosoma brucei genes encoding putative fatty acid synthesis enzymes are homologous to those encoding type II enzymes found in bacteria and organelles such as chloroplasts and mitochondria. It was therefore not surprising that triclosan, an inhibitor of type II enoyl-acyl carrier protein (enoyl-ACP) reductase, killed both procyclic forms and bloodstream forms of T. brucei in culture with 50% effective concentrations (EC 50 s) of 10 and 13 M, respectively. Triclosan also inhibited cell-free fatty acid synthesis, though much higher concentrations were required (EC 50 s of 100 to 200 M). Unexpectedly, 100 M triclosan did not affect the elongation of [ 3 H]laurate (C 12:0 ) to myristate (C 14:0 ) in cultured bloodstream form parasites, suggesting that triclosan killing of trypanosomes may not be through specific inhibition of enoyl-ACP reductase but through some other mechanism. Interestingly, 100 M triclosan did reduce the level of incorporation of [ 3 H]myristate into glycosyl phosphatidylinositol species (GPIs). Furthermore, we found that triclosan inhibited fatty acid remodeling in a cell-free assay in the same concentration range required for killing T. brucei in culture. In addition, we found that a similar concentration of triclosan also inhibited the myristate exchange pathway, which resides in a distinct subcellular compartment. However, GPI myristoylation and myristate exchange are specific to the bloodstream form parasite, yet triclosan kills both the bloodstream and procyclic forms. Therefore, triclosan killing may be due to a nonspecific perturbation of subcellular membrane structure leading to dysfunction in sensitive membrane-resident biochemical pathways.

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Section: Discussionmentioning

confidence: 99%

Multiple Triclosan Targets in Trypanosoma brucei

2004

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“…Such domains might be fewer or smaller when SOPS is replaced by the unsaturated variant DOPS. It is worth noting that the T m of a PS lipid is always higher than that of its PC counterpart with the same acyl chains (e.g., that of SOPC is ϳ6 to 9°C and that of SOPS is ϳ26°C [57]). We do therefore expect an incomplete lateral mixing of ePC and SOPS, although the space scale of such phase separation might be too small to be detected optically.…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylserine Lateral Organization Influences the Interaction of Influenza Virus Matrix Protein 1 with Lipid Membranes

Bobone

Hilsch

Storm

et al. 2017

J Virol

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Influenza A virus matrix protein 1 (M1) is an essential component involved in the structural stability of the virus and in the budding of new virions from infected cells. A deeper understanding of the molecular basis of virion formation and the budding process is required in order to devise new therapeutic approaches. We performed a detailed investigation of the interaction between M1 and phosphatidylserine (PS) (i.e., its main binding target at the plasma membrane [PM]), as well as the distribution of PS itself, both in model membranes and in living cells. To this end, we used a combination of techniques, including Förster resonance energy transfer (FRET), confocal microscopy imaging, raster image correlation spectroscopy, and number and brightness (N&B) analysis. Our results show that PS can cluster in segregated regions in the plane of the lipid bilayer, both in model bilayers constituted of PS and phosphatidylcholine and in living cells. The viral protein M1 interacts specifically with PS-enriched domains, and such interaction in turn affects its oligomerization process. Furthermore, M1 can stabilize PS domains, as observed in model membranes. For living cells, the presence of PS clusters is suggested by N&B experiments monitoring the clustering of the PS sensor lactadherin. Also, colocalization between M1 and a fluorescent PS probe suggest that, in infected cells, the matrix protein can specifically bind to the regions of PM in which PS is clustered. Taken together, our observations provide novel evidence regarding the role of PS-rich domains in tuning M1-lipid and M1-M1 interactions at the PM of infected cells.IMPORTANCE Influenza virus particles assemble at the plasma membranes (PM) of infected cells. This process is orchestrated by the matrix protein M1, which interacts with membrane lipids while binding to the other proteins and genetic material of the virus. Despite its importance, the initial step in virus assembly (i.e., M1-lipid interaction) is still not well understood. In this work, we show that phosphatidylserine can form lipid domains in physical models of the inner leaflet of the PM. Furthermore, the spatial organization of PS in the plane of the bilayer modulates M1-M1 interactions. Finally, we show that PS domains appear to be present in the PM of living cells and that M1 seems to display a high affinity for them.KEYWORDS influenza, assembly, confocal microscopy, fluorescence image analysis, lipid rafts, matrix protein, model membranes, phosphatidylserine, plasma membrane I nfluenza A virus (IAV) is a major burden to human health and remains a prominent cause of mortality worldwide (1, 2). Despite significant research efforts, detailed knowledge about the molecular mechanisms involved in IAV infection is still limited. A deeper understanding of the virus machinery and its interaction with the host is

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“…The early work on triclosan highlighted its effect on the bacterial membrane structures, particularly its distruptive effects on lipids and proteins. 98 A more recent line of enquiry has been to investigate the bacterial effl ux defence mechanism whereby harmful molecules are removed. 99 It has been reported that the 'upregulation' of the effl ux defence mechanism stimulated by sub-lethal levels of triclosan has resulted in some resistance to antibiotics.…”

Section: Microbial Resistancementioning

confidence: 99%