Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity

Tomek, P.; Hrouzek, Pavel; Kuzma, Marek; Sýkora, Jan; Fišer, R.; Černý, J.; Novák, Petr; Bártová, Simona; Šimek, Petr; Hof, Martin; Kavan, Daniel; Kopecký, Jiří

doi:https://dx.doi.org/10.1021/tx500382b

Number of the records: 1

Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity

1.

SYSNO ASEP	0445230
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity
Author(s)	Tomek, P. (CZ) Hrouzek, Pavel (MBU-M)_ORCID Kuzma, Marek (MBU-M)_{ORCID, RID} Sýkora, Jan (UFCH-W)_RID Fišer, R. (CZ) Černý, J. (CZ) Novák, Petr (MBU-M)_{RID, ORCID} Bártová, Simona (MBU-M) Šimek, Petr (BC-A)_{RID, ORCID} Hof, Martin (UFCH-W)_{RID, ORCID} Kavan, Daniel (MBU-M)_{RID, ORCID} Kopecký, Jiří (MBU-M)_ORCID
Source Title	Chemical Research in Toxicology - ISSN 0893-228X Roč. 28, č. 2 (2015), s. 216-224
Number of pages	9 s.
Language	eng - English
Country	US - United States
Keywords	BLUE-GREEN-ALGA ; CYCLIC-PEPTIDES ; LYNGBYA SP
Subject RIV	EE - Microbiology, Virology
Subject RIV - cooperation	J. Heyrovsky Institute of Physical Chemistry - Microbiology, Virology Biology Centre (since 2006) - Microbiology, Virology
R&D Projects	GPP503/12/P614 GA ČR - Czech Science Foundation (CSF)
	LH11129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED2.1.00/03.0110 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Institutional support	MBU-M - RVO:61388971 ; UFCH-W - RVO:61388955 ; BC-A - RVO:60077344
UT WOS	000349656100008
EID SCOPUS	84945361419
DOI	10.1021/tx500382b
Annotation	There is mounting evidence that cyanobacterial lipopeptides can kill mammalian cells, presenting a hazard to human health. Unfortunately, their mechanism of toxicity is poorly understood. We have isolated new cyclic undeca-lipopeptides muscotoxin A and B containing unique lipophilic residue 3-amino-2,5-dihydroxydecanoic acid (5-OH Ahdoa). Muscotoxin B was not used for biological studies due to its poor yield. Muscotoxin A was cytotoxic to YAC-1, Sp/2, and HeLa cancer cell lines (LC50 ranged from 9.9 to 13.2 mu M after 24 h of exposure), causing membrane damage and influx of calcium ions. Subsequently, we studied this lytic mechanism using synthetic liposomes with encapsulated fluorescent probes. Muscotoxin A permeabilized liposomes composed exclusively of phospholipids, demonstrating that no proteins or carbohydrates present in biomembranes are essential for its activity. Paradoxically, the permeabilization activity of muscotoxin A was mediated by a significant reduction in membrane surface fluidity (stiffening), the opposite of that caused by synthetic detergents and cytolytic lipopeptide puwainaphycin F. At 25 degrees C, muscotoxin A disrupted liposomes with and without cholesterol/sphingomyelin; however, at 37 degrees C, it was selective against liposomes with cholesterol/sphingomyelin. It appears that both membrane fluidity and organization can affect the lytic activity of muscotoxin A. Our findings strengthen the evidence that cyanobacterial lipopeptides specifically disrupt mammalian cell membranes and bring new insights into the mechanism of this effect.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2016

Number of the records: 1