scholarly journals Influence of Ca2+ Ions on the Activity of Lantibiotics Containing a Mersacidin-Like Lipid II Binding Motif

2009 ◽  
Vol 75 (13) ◽  
pp. 4427-4434 ◽  
Author(s):  
T. Böttiger ◽  
T. Schneider ◽  
B. Martínez ◽  
H.-G. Sahl ◽  
I. Wiedemann
Keyword(s):  
Antimicrobial Activity ◽  
Cell Wall ◽  
Mode Of Action ◽  
Cell Wall Biosynthesis ◽  
Binding Motif ◽  
Bacterial Membrane ◽  
Lipid Ii ◽  
Lacticin 3147 ◽  
Lacticin 481

ABSTRACT Mersacidin binds to lipid II and thus blocks the transglycosylation step of the cell wall biosynthesis. Binding of lipid II involves a special motif, the so-called mersacidin-lipid II binding motif, which is conserved in a major subgroup of lantibiotics. We analyzed the role of Ca2+ ions in the mode of action of mersacidin and some related peptides containing a mersacidin-like lipid II binding motif. We found that the stimulating effect of Ca2+ ions on the antimicrobial activity known for mersacidin also applies to plantaricin C and lacticin 3147. Ca2+ ions appear to facilitate the interaction of the lantibiotics with the bacterial membrane and with lipid II rather than being an essential part of a peptide-lipid II complex. In the case of lacticin 481, both the interaction with lipid II and the antimicrobial activity were Ca2+ independent.

scholarly journals Role of Lipid II and Membrane Thickness in the Mechanism of Action of the Lantibiotic Bovicin HC5

2011 ◽  
Vol 55 (11) ◽  
pp. 5284-5293 ◽  
Author(s):  
Aline Dias Paiva ◽  
Eefjan Breukink ◽  
Hilário Cuquetto Mantovani
Keyword(s):  
Mode Of Action ◽  
Pore Formation ◽  
Membrane Vesicles ◽  
Model Membranes ◽  
Binding Motif ◽  
Membrane Thickness ◽  
Content Type ◽  
Lipid Ii ◽  
Bovicin Hc5

ABSTRACTLantibiotics are antimicrobial peptides produced by Gram-positive bacteria, nisin being the most well-known member. Nisin inhibits peptidoglycan synthesis and forms pores at sensitive membranes upon interaction with lipid II, the essential bacterial cell wall precursor. Bovicin HC5, a bacteriocin produced byStreptococcus bovisHC5, has the putative N-terminal lipid II binding motif, and we investigated the mode of action of bovicin HC5 using both living bacteria and model membranes, with special emphasis on the role of lipid II. Bovicin HC5 showed activity againstStaphylococcus cohniiandStaphylococcus warneri, but bovicin HC5 hardly interfered with the membrane potential ofS. cohnii. In model membranes, bovicin HC5 was not able to cause carboxyfluorescein release or proton influx from DOPC vesicles containing lipid II. Bovicin HC5 blocked lipid II-dependent pore formation activity of nisin, and a high-affinity interaction with lipid II was observed (apparent binding constant [Ka] = 3.1 × 106M−1), with a 1:1 stoichiometry. In DOPC vesicles containing lipid II, bovicin HC5 was able to assemble with lipid II into a prepore-like structure. Furthermore, we observed pore formation activity of bovicin HC5, which was stimulated by the presence of lipid II, in thin membranes. Moreover, bovicin HC5 induced the segregation of lipid II into domains in giant model membrane vesicles. In conclusion, bovicin HC5 has a primary mode of action similar to that of nisin, but some differences regarding the pore-forming capacity were demonstrated.

Antimicrobial mechanism of lantibiotics

2012 ◽  
Vol 40 (6) ◽  
pp. 1528-1533 ◽  
Author(s):  
Mohammad R. Islam ◽  
Jun-ichi Nagao ◽  
Takeshi Zendo ◽  
Kenji Sonomoto
Keyword(s):  
Cell Wall ◽  
Pore Formation ◽  
Type A ◽  
Cell Wall Biosynthesis ◽  
Lipid Ii ◽  
Lacticin 3147 ◽  
Antimicrobial Mechanism ◽  
Formation Type ◽  
Target Membrane ◽  
Membrane Type

Lantibiotics are ribosomally synthesized antimicrobial peptides that commonly target the cell wall precursor lipid II during their antimicrobial mechanism and exert their inhibitory activity by (i) inhibition of cell wall biosynthesis, and (ii) stable pore formation in the target membrane. Type-A(I) (i.e. nisin) and two-component (i.e. lacticin 3147) lantibiotics initially interact with lipid II to stabilize the complex, which then proceeds to inhibit cell wall biosynthesis and pore formation. Type-A(II) (i.e. nukacin ISK-1) and type-B (i.e. mersacidin) lantibiotics also use lipid II as a docking molecule, but can only inhibit cell wall biosynthesis without forming pores. In the present paper, we review the antimicrobial mechanism of different types of lantibiotics, their current progress and future prospect.

The mode of action of the lantibiotic lacticin 3147 - a complex mechanism involving specific interaction of two peptides and the cell wall precursor lipid II

2006 ◽  
Vol 61 (2) ◽  
pp. 285-296 ◽  
Author(s):  
Imke Wiedemann ◽  
Tim Bottiger ◽  
Raquel R. Bonelli ◽  
Andre Wiese ◽  
Sven O. Hagge ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mode Of Action ◽  
Specific Interaction ◽  
Complex Mechanism ◽  
Lipid Ii ◽  
Lacticin 3147

scholarly journals Insights into the Mode of Action of Chitosan as an Antibacterial Compound

2008 ◽  
Vol 74 (12) ◽  
pp. 3764-3773 ◽  
Author(s):  
Dina Raafat ◽  
Kristine von Bargen ◽  
Albert Haas ◽  
Hans-Georg Sahl
Keyword(s):  
Antimicrobial Activity ◽  
Cell Wall ◽  
Cell Membrane ◽  
Mode Of Action ◽  
Membrane Lipids ◽  
Expression Profiles ◽  
Transcriptional Response ◽  
Response Analysis ◽  
Sequence Of Events ◽  
Wide Range

ABSTRACT Chitosan is a polysaccharide biopolymer that combines a unique set of versatile physicochemical and biological characteristics which allow for a wide range of applications. Although its antimicrobial activity is well documented, its mode of action has hitherto remained only vaguely defined. In this work we investigated the antimicrobial mode of action of chitosan using a combination of approaches, including in vitro assays, killing kinetics, cellular leakage measurements, membrane potential estimations, and electron microscopy, in addition to transcriptional response analysis. Chitosan, whose antimicrobial activity was influenced by several factors, exhibited a dose-dependent growth-inhibitory effect. A simultaneous permeabilization of the cell membrane to small cellular components, coupled to a significant membrane depolarization, was detected. A concomitant interference with cell wall biosynthesis was not observed. Chitosan treatment of Staphylococcus simulans 22 cells did not give rise to cell wall lysis; the cell membrane also remained intact. Analysis of transcriptional response data revealed that chitosan treatment leads to multiple changes in the expression profiles of Staphylococcus aureus SG511 genes involved in the regulation of stress and autolysis, as well as genes associated with energy metabolism. Finally, a possible mechanism for chitosan's activity is postulated. Although we contend that there might not be a single classical target that would explain chitosan's antimicrobial action, we speculate that binding of chitosan to teichoic acids, coupled with a potential extraction of membrane lipids (predominantly lipoteichoic acid) results in a sequence of events, ultimately leading to bacterial death.

scholarly journals Human β-Defensin 3 Inhibits Cell Wall Biosynthesis in Staphylococci

2010 ◽  
Vol 78 (6) ◽  
pp. 2793-2800 ◽  
Author(s):  
Vera Sass ◽  
Tanja Schneider ◽  
Miriam Wilmes ◽  
Christian Körner ◽  
Alessandro Tossi ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cell Wall ◽  
Host Defense ◽  
Transcriptional Response ◽  
Cell Wall Biosynthesis ◽  
Host Defense Peptides ◽  
Lipid Ii ◽  
Transmission Electron ◽  
Host Defense Peptide

ABSTRACT Human β-defensin 3 (hBD3) is a highly charged (+11) cationic host defense peptide, produced by epithelial cells and neutrophils. hBD3 retains antimicrobial activity against a broad range of pathogens, including multiresistant Staphylococcus aureus, even under high-salt conditions. Whereas antimicrobial host defense peptides are assumed to act by permeabilizing cell membranes, the transcriptional response pattern of hBD3-treated staphylococcal cells resembled that of vancomycin-treated cells (V. Sass, U. Pag, A. Tossi, G. Bierbaum, and H. G. Sahl, Int. J. Med. Microbiol. 298:619-633, 2008) and suggested that inhibition of cell wall biosynthesis is a major component of the killing process. hBD3-treated cells, inspected by transmission electron microscopy, showed localized protrusions of cytoplasmic contents, and analysis of the intracellular pool of nucleotide-activated cell wall precursors demonstrated accumulation of the final soluble precursor, UDP-MurNAc-pentapeptide. Accumulation is typically induced by antibiotics that inhibit membrane-bound steps of cell wall biosynthesis and also demonstrates that hBD3 does not impair the biosynthetic capacity of cells and does not cause gross leakage of small cytoplasmic compounds. In in vitro assays of individual membrane-associated cell wall biosynthesis reactions (MraY, MurG, FemX, and penicillin-binding protein 2 [PBP2]), hBD3 inhibited those enzymes which use the bactoprenol-bound cell wall building block lipid II as a substrate; quantitative analysis suggested that hBD3 may stoichiometrically bind to lipid II. We report that binding of hBD3 to defined, lipid II-rich sites of cell wall biosynthesis may lead to perturbation of the biosynthesis machinery, resulting in localized lesions in the cell wall as demonstrated by electron microscopy. The lesions may then allow for osmotic rupture of cells when defensins are tested under low-salt conditions.

scholarly journals Insights into In Vivo Activities of Lantibiotics from Gallidermin and Epidermin Mode-of-Action Studies

2006 ◽  
Vol 50 (4) ◽  
pp. 1449-1457 ◽  
Author(s):  
Raquel Regina Bonelli ◽  
Tanja Schneider ◽  
Hans-Georg Sahl ◽  
Imke Wiedemann
Keyword(s):  
Cell Wall ◽  
Pore Formation ◽  
Specific Interaction ◽  
Binding Motif ◽  
Membrane Thickness ◽  
Peptide Antibiotics ◽  
Intact Cells ◽  
Lipid Ii ◽  
A Cell

ABSTRACT The activity of lanthionine-containing peptide antibiotics (lantibiotics) is based on different killing mechanisms which may be combined in one molecule. The prototype lantibiotic nisin inhibits peptidoglycan synthesis and forms pores through specific interaction with the cell wall precursor lipid II. Gallidermin and epidermin possess the same putative lipid II binding motif as nisin; however, both peptides are considerably shorter (22 amino acids, compared to 34 in nisin). We demonstrate that in model membranes, lipid II-mediated pore formation by gallidermin depends on membrane thickness. With intact cells, pore formation was less pronounced than for nisin and occurred only in some strains. In Lactococcus lactis subsp. cremoris HP, gallidermin was not able to release K+, and a mutant peptide, [A12L]gallidermin, in which the ability to form pores was disrupted, was as potent as wild-type gallidermin, indicating that pore formation does not contribute to killing. In contrast, nisin rapidly formed pores in the L. lactis strain; however, it was approximately 10-fold less effective in killing. The superior activity of gallidermin in a cell wall biosynthesis assay may help to explain this high potency. Generally, it appears that the multiple activities of lantibiotics combine differently for individual target strains.

scholarly journals Oritavancin Exhibits Dual Mode of Action to Inhibit Cell-Wall Biosynthesis in Staphylococcus aureus

2008 ◽  
Vol 377 (1) ◽  
pp. 281-293 ◽  
Author(s):  
Sung Joon Kim ◽  
Lynette Cegelski ◽  
Dirk Stueber ◽  
Manmilan Singh ◽  
Evelyne Dietrich ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Mode Of Action ◽  
Cell Wall Biosynthesis ◽  
Dual Mode

scholarly journals An Engineered Double Lipid II Binding Motifs-Containing Lantibiotic Displays Potent and Selective Antimicrobial Activity against Enterococcus faecium

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Xinghong Zhao ◽  
Zhongqiong Yin ◽  
Eefjan Breukink ◽  
Gert N. Moll ◽  
Oscar P. Kuipers
Keyword(s):  
Antimicrobial Activity ◽  
Enterococcus Faecium ◽  
Binding Motif ◽  
Peptide Antibiotics ◽  
Antibiotic Resistant ◽  
Binding Motifs ◽  
New Approach ◽  
Content Type ◽  
Lipid Ii ◽  
Selective Antimicrobial Activity

ABSTRACT Lipid II is an essential precursor for bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two-lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e., HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against Enterococcus faecium than nisin(1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and the double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

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