Specific Interactions of Mycosubtilin with Cholesterol-Containing Artificial Membranes

Abstract

Mycosubtilin is a natural antimicrobial lipopeptide produced by Bacillus subtilis strains. It is characterized by its hemolytic and strong antifungal activities. Mycosubtilin interacts with the plasma membranes of sensitive cells. However, the molecular mechanisms of its biological activities have not been completely elucidated. Our purpose was therefore to analyze the interactions of mycosubtilin with biological membranes by using biomimetic membranes such as Langmuir monolayers and multilayers. Structural changes of mycosubtilin, involving its peptide backbone and the side chain of its tyrosyl residue, were observed when the lipopeptide was interacting with cholesterol-containing multilayers. The interactions of mycosubtilin with monolayers constituted by pure lipids and by phosholipid/cholesterol or phospholipid/sphingomyelin/cholesterol were also examined. An original behavior of mycosubtilin toward cholesterol-containing monolayers was found. However, this original behavior was lost when mycosubtilin was interacting with pure cholesterylacetate monolayers. This suggests the involvement of the alcohol group of cholesterol in mycosubtilin-cholesterol interactions within membranes. Moreover, mycosubtilin induced changes in the organization and morphology of cholesterol-containing monolayers, and large condensed domains with different levels of condensation appeared only in the case of DPPC/sphingomyelin/cholesterol monolayer.

Biocontrol Potentials of Antimicrobial Peptide Producing Bacillus Species: Multifaceted Antagonists for the Management of Stem Rot of Carnation Caused by Sclerotinia sclerotiorum

“…Kenig and Abrahame (1976) reported that bacilysin hinders glucosamine synthesis, which in turn hinders cell wall synthesis. Nasir and Besson (2011) reported that mycosubtilin of B. subtilis interacts with the plasma membranes of fungal cells. Hyphal abnormalities were observed on the mycelia of Pestalotiopsis euginae treated with cell free extracts of B. subtilis that contained iturin and surfactin (Lin et al, 2011).…”

Cyclic lipopeptides from Bacillus subtilis activate distinct patterns of defence responses in grapevine

“…We also found that plipastatin did not exhibit a refractory state profile, suggesting that, like surfactin, recognition of the molecule could be independent of a specific receptor and may involve direct perception at the plasma membrane level by a lipid‐driven process (Henry et al ., ). Mycosubtilin has been shown to interact with cholesterol, ergosterol and phospholipid membrane models (Nasir and Besson, , ; Nasir et al ., ), but it is not known whether this LP could interfere with plant plasma membranes, especially by forming pores and inducing important modifications of the membrane permeability, as demonstrated for fungal membranes (Nasir and Besson, ). Physiological relevance of LP‐driven elicitation was also confirmed by the use of K‐252a, a potent inhibitor of protein kinases in animals and plants (Ruegg and Burgess, ).…”

Conformational analyses of bacillomycin D, a natural antimicrobial lipopeptide, alone or in interaction with lipid monolayers at the air–water interface

“…Despite many works carried out on the understanding of the molecular mechanisms of biological activity of the other iturinic lipopeptides [6][7][8][9][10][11][12], there are only few limited analyses of the bacillomycin D interaction with the plasma membrane of target cells [13][14][15], and the comparison of its hemolytic activity with those of other iturinic lipopeptides did not allow us to determine a rule based on the amino acid composition of the different lipopeptides (Table 1).…”