The role of phospholipid composition and ergosterol presence in the adaptation of fungal membranes to harsh environmental conditions–membrane modeling study

Perczyk, Paulina; Wójcik, Aneta; Wydro, Paweł; Broniatowski, Marcin

doi:10.1016/j.bbamem.2019.183136

Cited by 19 publications

(12 citation statements)

References 58 publications

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“…These are rich in PC and PE phospholipids but also ergosterol (ERGO). Phosphatidylinositol (PI) is often present, followed by PS, and it is generally found in the outer leaflet of fungal membranes, whereas in mammalian cells, it is mostly located in the inner leaflet [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ]. With the exception of PC, CXJ interacts efficiently with bilayer composed of the most common fungal phospholipids: PE ( Figure 3 F, Figure 5 B and Figure 6 B) and PI ( Figure 3 K and Supplementary Figure S7 ), partially conserving the U-shaped structure ( Figure 4 F).…”

Section: Resultsmentioning

confidence: 99%

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

Ramos‐Martín

D’Amelio

2021

IJMS

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Esophageal cancer is an aggressive lethal malignancy causing thousands of deaths every year. While current treatments have poor outcomes, cecropinXJ (CXJ) is one of the very few peptides with demonstrated in vivo activity. The great interest in CXJ stems from its low toxicity and additional activity against most ESKAPE bacteria and fungi. Here, we present the first study of its mechanism of action based on molecular dynamics (MD) simulations and sequence-property alignment. Although unstructured in solution, predictions highlight the presence of two helices separated by a flexible hinge containing P24 and stabilized by the interaction of W2 with target biomembranes: an amphipathic helix-I and a poorly structured helix-II. Both MD and sequence-property alignment point to the important role of helix I in both the activity and the interaction with biomembranes. MD reveals that CXJ interacts mainly with phosphatidylserine (PS) but also with phosphatidylethanolamine (PE) headgroups, both found in the outer leaflet of cancer cells, while salt bridges with phosphate moieties are prevalent in bacterial biomimetic membranes composed of PE, phosphatidylglycerol (PG) and cardiolipin (CL). The antibacterial activity of CXJ might also explain its interaction with mitochondria, whose phospholipid composition recalls that of bacteria and its capability to induce apoptosis in cancer cells.

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Section: Resultsmentioning

confidence: 99%

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

Ramos‐Martín

D’Amelio

2021

IJMS

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“…albicans, which does not contain a relevant amount of such phospholipids, needs further analysis. This prompted us to investigate the behavior of BLP-3 in the presence of lipids typically found in fungal membranes in general and in Candida in particular: PE, PS, PI, and ergosterol. − …”

Section: Results and Discussionmentioning

confidence: 99%

Antimicrobial Bombinin-like Peptide 3 Selectively Recognizes and Inserts into Bacterial Biomimetic Bilayers in Multiple Steps

et al. 2021

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Bombinins are a wide family of antimicrobial peptides from Xenopus skin. By sequence clustering, we highlighted at least three families named A, B, and H, which might exert antibacterial activity by different modes of action. In this work, we study bombinin-like peptide 3 (BLP-3) as a nonhemolytic representative of the quite unexplored class A due to its appealing activity toward WHO-priority-list bacteria such as Neisseria, Pseudomonas aeruginosa, and Staphylococcus aureus. A marked preference for cardiolipin and phosphatidylglycerol head groups, typically found in bacteria, is proven with biomimetic membranes studied by liquid and solid NMR and MD simulations. BLP-3 gets structured upon interaction and penetrates deeply into the bilayer in two steps involving a superficial insertion of key side chains and subsequent internalization. All along the pathway, a fundamental role is played by lysine residues in the conserved region 11–19, which act in synergy with other key residues.

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“…Note that PE solutions must contain at least a small percentage of PC (see Material and methods section) for the correct assembly of liposomes [92][93][94][95][96][97][98][99]. The effect is conserved in the presence of ergosterol, which was added to PE liposomes to better model fungal membranes [100][101][102][103][104]. The presence of ergosterol slightly reduces the fluidification induced by Sesquin (Figure 2C), proportionally to its concentration (Figure S4).…”

Section: Studies With Mlvs Show Sesquin Preference For Fungal and Bac...mentioning

confidence: 99%

The potential of antifungal peptide Sesquin as natural food preservative

Ramos‐Martín¹,

Herrera‐León²,

Antonietti³

et al. 2022

Biochimie

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The role of phospholipid composition and ergosterol presence in the adaptation of fungal membranes to harsh environmental conditions–membrane modeling study

Cited by 19 publications

References 58 publications

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study

Antimicrobial Bombinin-like Peptide 3 Selectively Recognizes and Inserts into Bacterial Biomimetic Bilayers in Multiple Steps

The potential of antifungal peptide Sesquin as natural food preservative

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