scholarly journals Acylation of SC4 dodecapeptide increases bactericidal potency against Gram-positive bacteria, including drug-resistant strains

2004 ◽  
Vol 378 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Nathan A. LOCKWOOD ◽  
Judith R. HASEMAN ◽  
Matthew V. TIRRELL ◽  
Kevin H. MAYO
Keyword(s):  
Fatty Acid ◽  
Fluorescence Spectroscopy ◽  
Bactericidal Activity ◽  
Bacterial Cell ◽  
Membrane Surface ◽  
Peptide Amphiphiles ◽  
Helical Conformation ◽  
Gram Positive ◽  
Bacterial Membranes ◽  
Bactericidal Activities

We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal activities of the resultant SC4 ‘peptide-amphiphile’ molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), including S. aureus strains resistant to conventional antibiotics, but little or no increase in bactericidal activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fatty acid conjugation improved endotoxin (lipopolysaccharide) neutralization by 3- to 6-fold. Although acylation somewhat increased lysis of human erythrocytes, it did not increase lysis of endothelial cells, and the haemolytic effects occurred at concentrations 10- to 100-fold higher than those required for bacterial cell lysis. For insight into the mechanism of action of SC4 peptide-amphiphiles, CD, NMR and fluorescence spectroscopy studies were performed in micelle and liposome models of eukaryotic and bacterial cell membranes. CD indicated that SC4 peptide-amphiphiles had the strongest helical tendencies in liposomes mimicking bacterial membranes, and strong membrane integration of the SC4 peptide-amphiphiles was observed using tryptophan fluorescence spectroscopy under these conditions; results that correlated with the increased bactericidal activities of SC4 peptide-amphiphiles. NMR structural analysis in micelles demonstrated that the two-thirds of the peptide closest to the fatty acid tail exhibited a helical conformation, with the positively-charged side of the amphipathic helix interacting more with the model membrane surface. These results indicate that conjugation of a fatty acid chain to the SC4 peptide enhances membrane interactions, stabilizes helical structure in the membrane-bound state and increases bactericidal potency.

scholarly journals Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant Staphylococcus aureus

2005 ◽  
Vol 49 (3) ◽  
pp. 1127-1134 ◽  
Author(s):  
Deborah L. Higgins ◽  
Ray Chang ◽  
Dmitri V. Debabov ◽  
Joey Leung ◽  
Terry Wu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Bactericidal Activity ◽  
Bacterial Cell ◽  
Cell Membrane Potential ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Bacterial Cell Membrane

ABSTRACTThe emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms. As observed with vancomycin, telavancin inhibited late-stage peptidoglycan biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did the lipid II surrogate tripeptideN,N′-diacetyl-l-lysinyl-d-alanyl-d-alanine, with high affinity. Telavancin also perturbed bacterial cell membrane potential and permeability. In methicillin-resistantStaphylococcus aureus, telavancin caused rapid, concentration-dependent depolarization of the plasma membrane, increases in permeability, and leakage of cellular ATP and K+. The timing of these changes correlated with rapid , concentration-dependent loss of bacterial viability, suggesting that the early bactericidal activity of telavancin results from dissipation of cell membrane potential and an increase in membrane permeability. Binding and cell fractionation studies provided direct evidence for an interaction of telavancin with the bacterial cell membrane; stronger binding interactions were observed with the bacterial cell wall and cell membrane relative to vancomycin. We suggest that this multifunctional mechanism of action confers advantageous antibacterial properties.

scholarly journals In Vitro and Bactericidal Activities of ABT-492, a Novel Fluoroquinolone, against Gram-Positive and Gram-Negative Organisms

2004 ◽  
Vol 48 (7) ◽  
pp. 2771-2777 ◽  
Author(s):  
Laurel S. Almer ◽  
Jennifer B. Hoffrage ◽  
Erika L. Keller ◽  
Robert K. Flamm ◽  
Virginia D. Shortridge
Keyword(s):  
Bactericidal Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
The Family ◽  
Comparable Activity ◽  
Bactericidal Activities ◽  
Gram Negative Organisms

ABSTRACT In vitro activities of ABT-492, ciprofloxacin, levofloxacin, trovafloxacin, moxifloxacin, gatifloxacin, and gemifloxacin were compared. ABT-492 was more potent against quinolone-susceptible and -resistant gram-positive organisms, had activity similar to that of ciprofloxacin against certain members of the family Enterobacteriaceae, and had comparable activity against quinolone-susceptible, nonfermentative, gram-negative organisms. Bactericidal activity of ABT-492 was also evaluated.

Distinct bactericidal activities of bovine lactoferrin peptides LFampin 268–284 and LFampin 265–284: Asp-Leu-Ile makes a differenceThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 358-362 ◽  
Author(s):  
Marieke I.A. van der Kraan ◽  
Kamran Nazmi ◽  
Wim van ’t Hof ◽  
Arie V. Nieuw Amerongen ◽  
Enno C.I. Veerman ◽  
...  
Keyword(s):  
Review Process ◽  
Peer Review Process ◽  
Helical Conformation ◽  
Bovine Lactoferrin ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Bactericidal Activities ◽  
Α Helix ◽  
Selection Of

Two lactoferrampin (LFampin) peptides derived from bovine lactoferrin were compared with respect to their bactericidal activities. LFampin 265–284 killed a set of Gram-positive bacteria that were resistant to LFampin 268–284. The presence of 265Asp-Leu-267Ile did not simply lead to an overall increased potency, since higher concentrations of LFampin 265–284 than LFampin 268–284 were needed to kill the Gram-negative bacteria that were tested. The Asp-Leu-Ile sequence enhances the propensity of LFampin to adopt an α-helix, as shown by circular dichroism spectroscopy. These results suggest that the helical conformation of the peptide is an important determinant of the susceptibility of Gram-positive bacteria.

scholarly journals Listeriolysin S: A bacteriocin from Listeria monocytogenes that induces membrane permeabilization in a contact-dependent manner

2021 ◽  
Vol 118 (40) ◽  
pp. e2108155118
Author(s):  
Jazmín Meza-Torres ◽  
Mickaël Lelek ◽  
Juan J. Quereda ◽  
Martin Sachse ◽  
Giulia Manina ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Cell Membrane ◽  
Single Molecule ◽  
Bactericidal Activity ◽  
Bacterial Cell ◽  
Atp Release ◽  
Inhibition Mechanism ◽  
Dependent Manner ◽  
Bacterial Membranes ◽  
Bacterial Cell Membrane

Listeriolysin S (LLS) is a thiazole/oxazole–modified microcin (TOMM) produced by hypervirulent clones of Listeria monocytogenes. LLS targets specific gram-positive bacteria and modulates the host intestinal microbiota composition. To characterize the mechanism of LLS transfer to target bacteria and its bactericidal function, we first investigated its subcellular distribution in LLS-producer bacteria. Using subcellular fractionation assays, transmission electron microscopy, and single-molecule superresolution microscopy, we identified that LLS remains associated with the bacterial cell membrane and cytoplasm and is not secreted to the bacterial extracellular space. Only living LLS-producer bacteria (and not purified LLS-positive bacterial membranes) display bactericidal activity. Applying transwell coculture systems and microfluidic-coupled microscopy, we determined that LLS requires direct contact between LLS-producer and -target bacteria in order to display bactericidal activity, and thus behaves as a contact-dependent bacteriocin. Contact-dependent exposure to LLS leads to permeabilization/depolarization of the target bacterial cell membrane and adenosine triphosphate (ATP) release. Additionally, we show that lipoteichoic acids (LTAs) can interact with LLS and that LTA decorations influence bacterial susceptibility to LLS. Overall, our results suggest that LLS is a TOMM that displays a contact-dependent inhibition mechanism.

scholarly journals Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 542
Author(s):  
Gustavo Penteado Battesini Carretero ◽  
Greice Kelle Viegas Saraiva ◽  
Magali Aparecida Rodrigues ◽  
Sumika Kiyota ◽  
Marcelo Porto Bemquerer ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Biological Effects ◽  
Membrane Surface ◽  
Helical Structure ◽  
Helical Conformation ◽  
Property A ◽  
Cellular Processes ◽  
Double Stranded Dna ◽  
Low Toxicity

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm.

scholarly journals Photo-activated titanium surface confers time dependent bactericidal activity towards Gram positive and negative bacteria

2021 ◽  
pp. 111940
Author(s):  
Fei Pan ◽  
Stefanie Altenried ◽  
Flavia Zuber ◽  
Raphael S. Wagner ◽  
Yen-Hsun Su ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Titanium Surface ◽  
Time Dependent ◽  
Gram Positive

scholarly journals Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum

2021 ◽  
Author(s):  
Erum Malik ◽  
David A. Phoenix ◽  
Timothy J. Snape ◽  
Frederick Harris ◽  
Jaipaul Singh ◽  
...  
Keyword(s):  
Helical Structure ◽  
Food Preservation ◽  
Forming Process ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Membranes ◽  
Gram Positive Bacteria ◽  
Alkaline Conditions ◽  
Ph Dependent ◽  
Gram Negative Organisms

AbstractHere the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5–26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3–5.1 mN m−1) and lyse (↑ 15.1–32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1–23) in the N → C direction, with −  < µH > increasing overall from circa − 0.8 to − 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.

scholarly journals Molecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes

ACS Omega ◽  
2020 ◽  
Author(s):  
Aparajita Chakraborty ◽  
Elisey Kobzev ◽  
Jonathan Chan ◽  
Gayan Heruka de Zoysa ◽  
Vijayalekshmi Sarojini ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Bacterial Cell ◽  
Cell Membranes ◽  
Dynamics Simulation ◽  
Gram Positive ◽  
Gram Negative

Bactericidal activity characterization of an expanded porphyrin on Gram-positive bacteria.

2010 ◽  
Vol 150 ◽  
pp. 438-438 ◽  
Author(s):  
G. Rossi ◽  
R. Fedele ◽  
C. Comuzzi ◽  
D. Goi
Keyword(s):  
Bactericidal Activity ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Expanded Porphyrin
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