Antimicrobial peptide Temporin-L complexed with anionic cyclodextrins results in a potent and safe agent against sessile bacteria

Brancaccio, Diego; Pizzo, Elio; Cafaro, Valeria; Notomista, Eugenio; Lise, Federica De; Bosso, Andrea; Gaglione, Rosa; Merlino, Francesco; Novellino, Ettore; Ungaro, Francesca; Grieco, Paolo; Quaglia, Fabiana; Miro, Agnese; Carotenuto, Alfonso

doi:10.1016/j.ijpharm.2020.119437

Cited by 22 publications

(22 citation statements)

References 25 publications

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“…Consequently, even though we did not observe a reduction in the biofilm formation the molecule was able to kill bacteria embedded in the biofilm polymers. In this regard, TL (precursor of peptide 8 ) recently proved to be an effective agent able to affect P. aeruginosa PAO1 and methicillin-resistant S. aureus (MRSA) biofilms [ 21 ]. Similarly, peptide 8 due to positive charges distributed in the peptide sequence, might electrostatically interact with the extracellular matrix of biofilm, thus facilitating transition through this environment and improving its antimicrobial activity.…”

Section: Discussionmentioning

confidence: 99%

Novel Antimicrobial Peptide from Temporin L in The Treatment of Staphylococcus pseudintermedius and Malassezia pachydermatis in Polymicrobial Inter-Kingdom Infection

et al. 2020

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Interkingdom polymicrobial diseases are caused by different microorganisms that colonize the same niche, as in the case of yeast-bacteria coinfections. The latter are difficult to treat due the absence of any common therapeutic target for their elimination, both in animals and humans. Staphylococcus pseudintermedius and Malassezia pachydermatis belong to distinct kingdoms. They can colonize the same skin district or apparatus being the causative agents of fastidious pet animals’ pathologies. Here we analysed the antimicrobial properties of a panel of 11 peptides, derived from temporin L, against Malassezia pachydermatis. Only peptide 8 showed the best mycocidal activity at 6.25 μM. Prolonged application of peptide 8 did not cause M. pachydermatis drug-resistance. Peptide 8 was also able to inhibit the growth of Staphylococcus pseudintermedius, regardless of methicillin resistance, at 1.56 μM for methicillin-susceptible S. pseudintermedius (MSSP) and 6.25 μM for methicillin-resistant S. pseudintermedius (MRSP). Of interest, peptide 8 increased the susceptibility of MRSP to oxacillin. Oxacillin MIC value reduction was of about eight times when used in combination with peptide 8. Finally, the compound affected the vitality of bacteria embedded in S. pseudintermedius biofilm. In conclusion, peptide 8 might represent a valid therapeutic alternative in the treatment of interkingdom polymicrobial infections, also in the presence of methicillin-resistant bacteria.

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Section: Discussionmentioning

confidence: 99%

Novel Antimicrobial Peptide from Temporin L in The Treatment of Staphylococcus pseudintermedius and Malassezia pachydermatis in Polymicrobial Inter-Kingdom Infection

et al. 2020

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“…Anti-biofilm activity of r(P)ApoB L Ala peptide was tested on P. aeruginosa PAO1 and S. aureus MRSA WKZ-2 bacterial strains. Experiments were performed as previously described [ 9 , 11 , 12 , 49 ]. Briefly, bacteria were grown overnight in MHB (Becton Dickinson Difco), and then diluted to 1 × 10 8 CFU/mL in fresh 0.5× MHB containing increasing peptide concentrations (0–20 µM in the case of P. aeruginosa PAO1 and 0–2.5 µM in the case of S. aureus MRSA WKZ-2).…”

Section: Methodsmentioning

confidence: 99%

“…Recombinant ApoB-derived cryptides have been found to be endowed with a broad-range antimicrobial activity, being effective on both Gram-negative and Gram-positive bacterial strains, with a notable anti-biofilm activity and with the ability to synergistically act in combination with conventional antibiotics [ 9 ]. Moreover, peptides have been found to exhibit immunomodulatory properties, to target sensitive bacteria by depolarizing their cytoplasmic membrane, to display excellent cytotoxicity profiles, and not to select for bacterial resistance mechanisms [ 9 , 10 , 11 , 37 , 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of a Single Point Mutation on the Antimicrobial and Fibrillogenic Properties of Cryptides from Human Apolipoprotein B

et al. 2021

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Host defense peptides (HDPs) are gaining increasing interest, since they are endowed with multiple activities, are often effective on multidrug resistant bacteria and do not generally lead to the development of resistance phenotypes. Cryptic HDPs have been recently identified in human apolipoprotein B and found to be endowed with a broad-spectrum antimicrobial activity, with anti-biofilm, wound healing and immunomodulatory properties, and with the ability to synergistically act in combination with conventional antibiotics, while being not toxic for eukaryotic cells. Here, a multidisciplinary approach was used, including time killing curves, differential scanning calorimetry, circular dichroism, ThT binding assays, and transmission electron microscopy analyses. The effects of a single point mutation (Pro → Ala in position 7) on the biological properties of ApoB-derived peptide r(P)ApoBLPro have been evaluated. Although the two versions of the peptide share similar antimicrobial and anti-biofilm properties, only r(P)ApoBLAla peptide was found to exert bactericidal effects. Interestingly, antimicrobial activity of both peptide versions appears to be dependent from their interaction with specific components of bacterial surfaces, such as LPS or LTA, which induce peptides to form β-sheet-rich amyloid-like structures. Altogether, obtained data indicate a correlation between ApoB-derived peptides self-assembling state and their antibacterial activity.

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“… 29 , 30 Functional investigations demonstrated that 7 was able to interfere with E. coli divisome machinery, binding to the FtsZ protein ( K D = 17.4 ± 0.8 nM) and inhibiting its GTPase activity. 31 TL has proven to mediate a strong antibiofilm activity against P. aeruginosa PAO1 and methicillin-resistant S. aureus , 32 , 33 but the underlying molecular mechanism is still unknown. The resulting effect might be due to either interference with biofilm formation or downregulation of genes involved in the synthesis of biofilm components.…”

Section: Introductionmentioning

confidence: 99%

First-in-Class Cyclic Temporin L Analogue: Design, Synthesis, and Antimicrobial Assessment

et al. 2021

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The pharmacodynamic and pharmacokinetic properties of bioactive peptides can be modulated by introducing conformational constraints such as intramolecular macrocyclizations, which can involve either the backbone and/or side chains. Herein, we aimed at increasing the α-helicity content of temporin L, an isoform of an intriguing class of linear antimicrobial peptides (AMPs), endowed with a wide antimicrobial spectrum, by the employment of diverse side-chain tethering strategies, including lactam, 1,4-substituted [1,2,3]-triazole, hydrocarbon, and disulfide linkers. Our approach resulted in a library of cyclic temporin L analogues that were biologically assessed for their antimicrobial, cytotoxic, and antibiofilm activities, leading to the development of the first-in-class cyclic peptide related to this AMP family. Our results allowed us to expand the knowledge regarding the relationship between the α-helical character of temporin derivatives and their biological activity, paving the way for the development of improved antibiotic cyclic AMP analogues.

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Antimicrobial peptide Temporin-L complexed with anionic cyclodextrins results in a potent and safe agent against sessile bacteria

Cited by 22 publications

References 25 publications

Novel Antimicrobial Peptide from Temporin L in The Treatment of Staphylococcus pseudintermedius and Malassezia pachydermatis in Polymicrobial Inter-Kingdom Infection

Novel Antimicrobial Peptide from Temporin L in The Treatment of Staphylococcus pseudintermedius and Malassezia pachydermatis in Polymicrobial Inter-Kingdom Infection

Impact of a Single Point Mutation on the Antimicrobial and Fibrillogenic Properties of Cryptides from Human Apolipoprotein B

First-in-Class Cyclic Temporin L Analogue: Design, Synthesis, and Antimicrobial Assessment

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