Development of a Potent Antimicrobial Peptide With Photodynamic Activity.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang D
PROVIDER: S-EPMC8203924 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Phthalocyanines (Pcs) are a group of promising photosensitizers for use in photodynamic therapy (PDT). However, their extremely low solubility and their strong tendency to aggregate in aqueous solution greatly restrict their application. Conjugation of Pc macrocycles with peptide ligands could be a very useful strategy to optimize the physical properties of Pcs not only by increasing their water solubility and reducing their aggregation but also by endowing the conjugates with a tumor-targeting capability. To develop highly potent photosensitizers for tumor PDT, we prepared new peptide-conjugated photosensitizers using silicon Pc (SiPc), which has much higher photodynamic activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or simply cRGD) as the peptide moiety. A polyethylene glycol linker and an extra carboxylic acid group were also tested for introduction into the conjugates to optimize the conjugate structure. The conjugates' photophysical and photodynamic behaviors were then carefully evaluated and compared using in vitro and in vivo experiments. One of the prepared conjugates, RGD-(Linker)2-Glu-SiPc, showed excellent physical properties and photodynamic activity, with an EC50 (half maximal effective concentration) of 10-20 nM toward various cancer cells. This conjugate eradicated human glioblastoma U87-MG tumors in a xenograft murine tumor model after only one dose of photodynamic treatment, with no tumor regrowth during observation for up to 35 days. The conjugate RGD-(Linker)2-Glu-SiPc thus showed highly promising potential for use in tumor treatment.
| S-EPMC5771339 | biostudies-literature
Project description:In the past few years, the World Health Organization has been warning that the post-antibiotic era is an increasingly real threat. The rising and disseminated resistance to antibiotics made mandatory the search for new drugs and/or alternative therapies that are able to eliminate resistant microorganisms and impair the development of new forms of resistance. In this context, antimicrobial photodynamic therapy (aPDT) and helical cationic antimicrobial peptides (AMP) are highlighted for the treatment of localized infections. This study aimed to combine the AMP aurein 1.2 to aPDT using Enterococcus faecalis as a model strain. Our results demonstrate that the combination of aPDT with aurein 1.2 proved to be a feasible alternative capable of completely eliminating E. faecalis employing low concentrations of both PS and AMP, in comparison with the individual therapies. Aurein 1.2 is capable of enhancing the aPDT activity whenever mediated by methylene blue or chlorin-e6, but not by curcumin, revealing a PS-dependent mechanism. The combined treatment was also effective against different strains; noteworthy, it completely eliminated a vancomycin-resistant strain of Enterococcus faecium. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections as an alternative to antibiotics.
| S-EPMC5844988 | biostudies-literature
Project description:Conventional antibiotics are facing strong microbial resistance that has recently reached critical levels. This situation is leading to significantly reduced therapeutic potential of a huge proportion of antimicrobial agents currently used in clinical settings. Antimicrobial peptides (AMPs) could provide the medical community with an alternative strategy to traditional antibiotics for combating microbial resistance. However, the development of AMPs into clinically useful antibiotics is hampered by their relatively low stability, toxicity, and high manufacturing costs. In this study, a novel in-house-designed potent ultrashort AMP named RBRBR was encapsulated into chitosan-based nanoparticles (CS-NPs) based on the ionotropic gelation method. The encapsulation efficacy reported for RBRBR into CS-NPs was 51.33%, with a loading capacity of 10.17%. The release kinetics of RBRBR from the nanocarrier exhibited slow release followed by progressive linear release for 14 days. The antibacterial kinetics of RBRBR-CS-NPs was tested against four strains of Staphylococcus aureus for 4 days, and the developed RBRBR-CS-NPs exhibited a 3-log decrease in the number of colonies when compared to CS-NP and a 5-log decrease when compared to control bacteria. The encapsulated peptide NP formulation managed to limit the toxicity of the free peptide against both mammalian cells and human erythrocytes. Additionally, the peptide NPs demonstrated up to 98% inhibition of biofilm formation when tested against biofilm-forming bacteria. Loading RBRBR into CS-NPs could represent an innovative approach to develop delivery systems based on NP technology for achieving potent antimicrobial effects against multidrug-resistant and biofilm-forming bacteria, with negligible systemic toxicity and reduced synthetic costs, thereby overcoming the obstructions to clinical development of AMPs.
| S-EPMC5679673 | biostudies-literature
Project description:Antibiotic resistance is an important issue affecting humans and livestock. Antimicrobial peptides are promising alternatives to antibiotics. In this study, the antimicrobial peptide Css54, isolated from the venom of C. suffuses, was found to exhibit antimicrobial activity against bacteria such as Listeria monocytogenes, Streptococcus suis, Campylobacter jejuni, and Salmonella typhimurium that cause zoonotic diseases. Moreover, the cytotoxicity and hemolytic activity of Css54 was lower than that of melittin isolated from bee venom. Circular dichroism assays showed that Css54 has an α-helix structure in an environment mimicking that of bacterial cell membranes. We examined the effect of Css54 on bacterial membranes using N-phenyl-1-naphthylamine, 3,3'-dipropylthiadicarbbocyanine iodides, SYTOX green, and propidium iodide. Our findings suggest that the Css54 peptide kills bacteria by disrupting the bacterial membrane. Moreover, Css54 exhibited antibiofilm activity against L. monocytogenes. Thus, Css54 may be useful as an alternative to antibiotics in humans and animal husbandry.
| S-EPMC7699533 | biostudies-literature
Project description:Pardaxin is an antimicrobial peptide of 33 amino acids, originally isolated from marine fish. We previously demonstrated that pardaxin has anti-tumor activity against murine fibrosarcoma, both in vitro and in vivo. In this study, we examined the anti-tumor activity, toxicity profile, and maximally-tolerated dose of pardaxin treatment in dogs with different types of refractory tumor. Local injection of pardaxin resulted in a significant reduction of perianal gland adenoma growth between 28 and 38 days post-treatment. Surgical resection of canine histiocytomas revealed large areas of ulceration, suggesting that pardaxin acts like a lytic peptide. Pardaxin treatment was not associated with significant variations in blood biochemical parameters or secretion of immune-related proteins. Our findings indicate that pardaxin has strong therapeutic potential for treating perianal gland adenomas in dogs. These data justify the veterinary application of pardaxin, and also provide invaluable information for veterinary medicine and future human clinical trials.
| S-EPMC4385852 | biostudies-literature
Project description:AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high ?-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents.
| S-EPMC4897634 | biostudies-literature
Project description:(1) Background: Antimicrobial resistance represents an urgent health dilemma facing the global human population. The development of novel antimicrobial agents is needed to face the rising number of resistant bacteria. Ultrashort antimicrobial peptides (USAMPs) are considered promising antimicrobial agents that meet the required criteria of novel antimicrobial drug development. (2) Methods: Alapropoginine was rationally designed by incorporating arginine (R), biphenylalanine (B), and naproxen to create an ultrashort hexapeptide. The antimicrobial activity of alapropoginine was evaluated against different strains of bacteria. The hemolytic activity of alapropoginine was also investigated against human erythrocytes. Finally, synergistic studies with antibiotics were performed using the checkerboard technique and the determination of the fractional inhibitory index. (3) Results: Alapropoginine displayed potent antimicrobial activities against reference and multi-drug-resistant bacteria with MIC values of as low as 28.6 µg/mL against methicillin-resistant S. aureus. Alapropoginine caused negligible toxicity toward human red blood cells. Moreover, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their antimicrobial concentrations. (4) Conclusions: The present study indicates that alapropoginine exhibits promising antimicrobial activity against reference and resistant strains of bacteria with negligible hemolytic activity. Additionally, the peptide displays synergistic or additive effects when combined with several antibiotics.
| S-EPMC8231522 | biostudies-literature
Project description:BackgroundClostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections.MethodsPACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29.ResultsThree PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT.ConclusionThis innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon.
| S-EPMC4551672 | biostudies-literature
Project description:Methicillin-resistant Staphylococcus aureus (MRSA), a major scourge in skin and soft-tissue infections, expresses surface-bound haemoprotein receptors that can be exploited for the targeted delivery of photosensitizers. We have developed a nanosized agent for targeted antimicrobial photodynamic therapy (aPDT), comprised of GaPpIX (a hemin analog with potent photosensitizer activity) encapsulated in haemoglobin (GaHb), mounted on 10 nm Ag nanoparticles (AgNPs). The average GaHb-AgNP contains 28 GaPpIX units stabilized by Hb αβ-dimer units. Eradication (>6-log reduction) of S. aureus and MRSA can be achieved by a 10-second exposure to 405 nm irradiation from a light-emitting diode (LED) array (140 mW cm-2), with GaHb-AgNP loadings as low as 5.6 μg mL-1 for S. aureus and 16.6 μg mL-1 for MRSA, corresponding to nanomolar levels of GaPpIX. This reduction in bacterial count is several orders of magnitude greater than that of GaHb or free GaPpIX on a per mole basis. The GaHb-AgNP platform is also effective against persister MRSA and intracellular MRSA, and can provide comparable levels of aPDT with a 15-minute irradiation by an inexpensive compact fluorescent lightbulb. Collateral phototoxicity to keratinocytes (HaCaT cells) is low at the GaHb-AgNP concentrations and fluences used for aPDT. GaHb adsorbed on 10 nm AgNPs is much more potent than that on 40 nm AgNPs or 10 nm AuNPs, indicating that both size and plasmon-resonant coupling are important factors for enhanced aPDT. Electron microscopy analysis reveals that GaHb-AgNPs are not readily internalized by S. aureus but remain attached to the bacterial cell wall, the likely target of photo-oxidative damage.
| S-EPMC7663423 | biostudies-literature
Project description:Natural antimicrobial peptides (AMPs) are potential antibiotic alternatives. Marine crustaceans are thought to generate more powerful and various AMPs to protect themselves from infections caused by pathogenic microorganisms in their complex aquatic habitat, thus becoming one of the most promising sources of AMPs or other bioactive substances. In the study, a novel protein was identified as an interacting partner of male-specific AMP SCY2 in Scylla paramamosain and named scyreprocin. The recombinant product of scyreprocin (rScyreprocin) was successfully expressed in Escherichia coli. rScyreprocin exerted potent, broad-spectrum antifungal, antibacterial, and anti-biofilm activity (minimum inhibitory concentrations from 0.5 to 32 ?M) through differential modes of action, including disruption of cell membrane integrity and induction of cell apoptosis, and has rapid bactericidal (in 0.5-2 h) and fungicidal (in 8-10 h) kinetics. In addition to its fungicidal activity against planktonic fungi, rScyreprocin also prevented the adhesion of fungal cells, inhibited biofilm formation, and eradicated the mature biofilms. Moreover, rScyreprocin showed a profound inhibitory effect on spore germination of Aspergillus spp. (minimum inhibitory concentrations from 4 to 8 ?M). This peptide was not cytotoxic to murine and mammalian cells and could increase the survival rate of Oryzias melastigma under the challenge of Vibrio harveyi. Taken together, the novel AMP scyreprocin would be a promising alternative to antibiotics used in aquaculture and medicine.
| S-EPMC7396596 | biostudies-literature