Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus

Shurko, James; Galega, Ralph; Li, Chuxi; Lee, Grace C.

doi:10.1038/s41429-018-0090-7

Cited by 44 publications

(34 citation statements)

References 19 publications

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“…LL37 is amphiphilic in nature with hydrophobic and hydrophilic residues aligned on opposite sides of the peptide. This facilitates their penetration through the cell membrane [72], which results in inhibition of nucleic acid and protein biosynthesis, followed by leakage of the cell cytoplasm into the extracellular space, causing bacteria death [73]. Although the action of LL37 against Gram-negative bacteria is very similar to that described against Gram-positive bacteria, the rate at which cytoplasmic permeabilization occurs is superior.…”

Section: Cell-wall Disruption: Mechanisms Of Actionmentioning

confidence: 99%

Activity of Specialized Biomolecules against Gram-Positive and Gram-Negative Bacteria

et al. 2020

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The increased resistance of bacteria against conventional pharmaceutical solutions, the antibiotics, has raised serious health concerns. This has stimulated interest in the development of bio-based therapeutics with limited resistance, namely, essential oils (EOs) or antimicrobial peptides (AMPs). This study envisaged the evaluation of the antimicrobial efficacy of selected biomolecules, namely LL37, pexiganan, tea tree oil (TTO), cinnamon leaf oil (CLO) and niaouli oil (NO), against four bacteria commonly associated to nosocomial infections: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa. The antibiotic vancomycin and silver nanoparticles (AgNPs) were used as control compounds for comparison purposes. The biomolecules were initially screened for their antibacterial efficacy using the agar-diffusion test, followed by the determination of minimal inhibitory concentrations (MICs), kill-time kinetics and the evaluation of the cell morphology upon 24 h exposure. All agents were effective against the selected bacteria. Interestingly, the AgNPs required a higher concentration (4000–1250 μg/mL) to induce the same effects as the AMPs (500–7.8 μg/mL) or EOs (365.2–19.7 μg/mL). Pexiganan and CLO were the most effective biomolecules, requiring lower concentrations to kill both Gram-positive and Gram-negative bacteria (62.5–7.8 μg/mL and 39.3–19.7 μg/mL, respectively), within a short period of time (averaging 2 h 15 min for all bacteria). Most biomolecules apparently disrupted the bacteria membrane stability due to the observed cell morphology deformation and by effecting on the intracellular space. AMPs were observed to induce morphological deformations and cellular content release, while EOs were seen to split and completely envelope bacteria. Data unraveled more of the potential of these new biomolecules as replacements for the conventional antibiotics and allowed us to take a step forward in the understanding of their mechanisms of action against infection-related bacteria.

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Section: Cell-wall Disruption: Mechanisms Of Actionmentioning

confidence: 99%

Activity of Specialized Biomolecules against Gram-Positive and Gram-Negative Bacteria

et al. 2020

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“…5 It has also been reported previously that AMP such as LL-37 can synergize with conventional antibiotics for bacterial killing. 34,35 Therefore, we conducted studies to determine whether MSC CM contains factors that synergize with or exhibit additive bactericidal activity with conventional antibiotics, and to determine whether these effects are limited to only certain classes of common antibiotics.…”

Section: Msc CM Acts Synergistically With Antibiotics To Generate Bmentioning

confidence: 99%

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Chow

Johnson

Impastato

et al. 2019

Stem Cells Translational Medicine

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Mesenchymal stem cells (MSC) have been shown to improve wound healing and sup-press inflammatory immune responses. Newer research also indicates that MSC exhibit antimicrobial activity, although the mechanisms underlying this activity have not been fully elucidated. Therefore, we conducted in vitro and in vivo studies to examine the ability of resting and activated MSC to kill bacteria, including multidrug resistant strains. We investigated direct bacterial killing mechanisms and the interaction of MSC with host innate immune responses to infection. In addition, the activity of MSC against chronic bacterial infections was investigated in a mouse biofilm infection model. We found that MSC exhibited high levels of spontaneous direct bactericidal activity in vitro. Moreover, soluble factors secreted by MSC inhibited Staphylococcus aureus biofilm formation in vitro and disrupted the growth of established biofilms. Secreted factors from MSC also elicited synergistic killing of drug-resistant bacteria when combined with several major classes of antibiotics. Other studies demonstrated interactions of activated MSC with host innate immune responses, including triggering of neutrophil extracellular trap formation and increased phagocytosis of bacteria. Finally, activated MSC administered systemically to mice with established S. aureus biofilm infections significantly reduced bacterial numbers at the wound site and improved wound healing when combined with antibiotic therapy. These results indicate that MSC generate multiple direct and indirect, immunologically mediated antimicrobial activities that combine to help eliminate chronic bacterial infections when the cells are administered therapeutically.

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“…Properties possibly being relevant for therapeutic use, such as antibiotic synergism, a spectrum of activity against other E. coli strains, activity against clinical isolates and stability in the presence of human sera, were thus evaluated. No peptide was synergistic for ciprofloxacin or gentamicin, showing that the combined administration of these antibiotics offered no therapeutic advantage; only an additive effect could be appreciated, i.e., the sum of individual activities [ 43 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…The checkerboard method was used for evaluating peptide antibacterial activity in combination with antibiotics [ 43 ]. The peptides at different concentrations (1:2 dilutions from 2 × MIC to 0.03 × MIC) in absence or in combination with different antibiotics and concentrations (gentamicin or ciprofloxacin) were added to a 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

Shorter Antibacterial Peptide Having High Selectivity for E. coli Membranes and Low Potential for Inducing Resistance

et al. 2020

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Antimicrobial peptides (AMPs) have been recognised as a significant therapeutic option for mitigating resistant microbial infections. It has been found recently that Plasmodium falciparum-derived, 20 residue long, peptide 35409 had antibacterial and haemolytic activity, making it an AMP having reduced selectivity, and suggesting that it should be studied more extensively for obtaining new AMPs having activity solely targeting the bacterial membrane. Peptide 35409 was thus used as template for producing short synthetic peptides (<20 residues long) and evaluating their biological activity and relevant physicochemical characteristics for therapeutic use. Four of the sixteen short peptides evaluated here had activity against E. coli without any associated haemolytic effects. The 35409-1 derivative (17 residues long) had the best therapeutic characteristics as it had high selectivity for bacterial cells, stability in the presence of human sera, activity against E. coli multiresistant clinical isolates and was shorter than the original sequence. It had a powerful membranolytic effect and low potential for inducing resistance in bacteria. This peptide’s characteristics highlighted its potential as an alternative for combating infection caused by E. coli multiresistant bacteria and/or for designing new AMPs.

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Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination with vancomycin against S. aureus

Cited by 44 publications

References 19 publications

Activity of Specialized Biomolecules against Gram-Positive and Gram-Negative Bacteria

Activity of Specialized Biomolecules against Gram-Positive and Gram-Negative Bacteria

Antibacterial activity of human mesenchymal stem cells mediated directly by constitutively secreted factors and indirectly by activation of innate immune effector cells

Shorter Antibacterial Peptide Having High Selectivity for E. coli Membranes and Low Potential for Inducing Resistance

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