Browsing by Author "Bessa, Lucinda J."
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- Boosting cosmeceutical peptides: coupling imidazolium-based ionic liquids to pentapeptide-4 originates new leads with antimicrobial and collagenesis-inducing activitiesPublication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Aguiar, Luísa; Ferraz, Ricardo; Monteiro, Cláudia; Martins, M. Cristina L.; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaFollowing our previous reports on dual-action antibacterial and collagenesis-inducing hybrid peptide constructs based on “pentapeptide-4” (PP4, with amino acid sequence KTTKS), whose N-palmitoyl derivative is the well-known cosmeceutical ingredient Matrixyl, herein we disclose novel ionic liquid/PP4 conjugates (IL-KTTKS). These conjugates present potent activity against either antibiotic-susceptible strains or multidrug resistant clinical isolates of both Gram-positive and Gram-negative bacterial species belonging to the so-called “ESKAPE” group of pathogens. Noteworthy, their antibacterial activity is preserved in simulated wound fluid, which anticipates an effective action in the setting of a real wound bed. Moreover, their collagenesis-inducing effects in vitro are comparable to or stronger than those of Matrixyl. Altogether, IL-KTTKS exert a triple antibacterial, antifungal, and collagenesis-inducing action in vitro. These findings provide solid grounds for us to advance IL-KTTKS conjugates as promising leads for future development of topical treatments for complicated skin and soft tissue infections (cSSTI). Further studies are envisaged to incorporate IL-conjugates into suitable nanoformulations, to reduce toxicity and/or improve resistance to proteolytic degradation.
- “Clicking” an ionic liquid to a potent antimicrobial peptide: on the route towards improved stabilityPublication . Gomes, Ana; Bessa, Lucinda J.; Correia, Patrícia; Fernandes, Iva; Ferraz, Ricardo; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaA covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via “click” chemistry, and found to retain the parent peptide’s activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.
- Disclosure of a promising lead to tackle complicated skin and skin structure infections: antimicrobial and antibiofilm actions of peptide PP4-3.1Publication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Ferraz, Ricardo; Monteiro, Cláudia; Martins, M. Cristina L.; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaEfficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant S. aureus (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its N-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and Candida spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against S. aureus in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of Candida fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.
- Neofiscalin A and fiscalin C are potential novel indole alkaloid alternatives for the treatment of multidrug-resistant Gram-positive bacterial infectionsPublication . Bessa, Lucinda J.; Buttachon, Suradet; Dethoup, Tida; Martins, Rosario; Vasconcelos, Vitor; Kijjoa, Anake; Martins da Costa, PauloTen indole alkaloids were obtained from the marine sponge-associated fungus Neosartorya siamensis KUFA 0017. We studied the antimicrobial properties of these and of three other compounds previously isolated from the soil fungus N. siamensis KUFC 6349. Only neofiscalin A showed antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE); with a minimum inhibitory concentration (MIC) of 8 μg mL(-1) against both strains. Another compound, fiscalin C, presented synergistic activity against MRSA when combined with oxacillin, although alone showed no antibacterial effect. Moreover, neofiscalin A, when present at sub-MICs, hampered the ability of both MRSA and VRE strains to form a biofilm. Additionally, the biofilm inhibitory concentration values of neofiscalin A against the MRSA and VRE isolates were 96 and 80 μg mL(-1), respectively. At a concentration of 200 μg mL(-1), neofiscalin A was able to reduce the metabolic activity of the biofilms by ∼50%. One important fact is that our results also showed that neofiscalin A had no cytotoxicity against a human brain capillary endothelial cell line.
- Quaternized cashew gum: An anti-staphylococcal and biocompatible cationic polymer for biotechnological applicationsPublication . Quelemes, Patrick V.; Araújo, Alyne R. de; Plácido, Alexandra; Delerue-Matos, Cristina; Maciel, Jeanny S.; Bessa, Lucinda J.; Ombredane, Alicia S.; Joanitti, Graziella A.; Soares, Maria José dos S.; Eaton, Peter; Silva, Durcilene A. da; Leite, José Roberto S.A.Chemical modifications to cashew gum (CG) structure have been previously reported to obtain new physicochemical characteristics, however until now there were no reports of modifications by introduction of new functional groups to add cationic character. This study presents a quaternization route for CG using a quaternary ammonium reagent. The chemical features of the quaternized cashew gum derivatives (QCG) were analyzed by: FTIR, elemental analysis, degree of substitution, Zeta potential, 1H NMR and 1H-13C correlation (HSQC). QCG were evaluated for their anti-staphylococcal activity by determining minimum inhibitory and bactericidal concentrations against pathogenic Staphylococcus spp. and by imaging using atomic force microscopy. Moreover, the mammalian cell biocompatibility were also assessed through hemolytic and cell toxicity assays. QCG presented promising antimicrobial activity against methicillin-resistant S. aureus and biocompatibility on tested cells. These results show that QCG could be a promising tool in the development of biomaterials with an anti-septic action.
- Quaternized cashew gum: An anti-staphylococcal and biocompatible cationic polymer for biotechnological applicationsPublication . Quelemes, Patrick V.; Araújo, Alyne R. de; Plácido, Alexandra; Delerue-Matos, Cristina; Maciel, Jeanny S.; Bessa, Lucinda J.; Ombredane, Alicia S.; Joanitti, Graziella A.; Soares, Maria José dos S.; Eaton, Peter; Silva, Durcilene A. da; Leite, José Roberto S.A.Chemical modifications to cashew gum (CG) structure have been previously reported to obtain new physicochemical characteristics, however until now there were no reports of modifications by intro-duction of new functional groups to add cationic character. This study presents a quaternization route for CG using a quaternary ammonium reagent. The chemical features of the quaternized cashew gum derivatives (QCG) were analyzed by: FTIR, elemental analysis, degree of substitution, Zeta potential, 1H NMR and 1H-13C correlation (HSQC). QCG were evaluated for their anti-staphylococcal activity by deter-mining minimum inhibitory and bactericidal concentrations against pathogenic Staphylococcus spp. and by imaging using atomic force microscopy. Moreover, the mammalian cell biocompatibility were also assessed through hemolytic and cell toxicity assays. QCG presented promising antimicrobial activity against methicillin-resistant S. aureus and biocompatibility on tested cells. These results show that QCG could be a promising tool in the development of biomaterials with an anti-septic action.
- Structure and function of a novel antioxidant peptide from the skin of tropical frogsPublication . Barbosa, Eder Alves; Oliveira, Ana; Plácido, Alexandra; Socodato, Renato; Portugal, Camila C.; Mafud, Ana Carolina; Ombredane, Alicia S.; Moreira, Daniel C.; Vale, Nuno; Bessa, Lucinda J.; Joanitti, Graziella A.; Alves, Cláudia; Gomes, Paula; Delerue-Matos, Cristina; Mascarenhas, Yvonne Primerano; Marani, Mariela M.; Relvas, João B.; Pintado, Manuela; Leite, José Roberto S.A.The amphibian skin plays an important role protecting the organism from external harmful factors such as microorganisms or UV radiation. Based on biorational strategies, many studies have investigated the cutaneous secretion of anurans as a source of bioactive molecules. By a peptidomic approach, a novel antioxidant peptide (AOP) with in vitro free radical scavenging ability was isolated from Physalaemus nattereri. The AOP, named antioxidin-I, has a molecular weight [M+H]+ = 1543.69Da and a TWYFITPYIPDK primary amino acid sequence. The gene encoding the antioxidin-I precursor was expressed in the skin tissue of three other Tropical frog species: Phyllomedusa tarsius, P. distincta and Pithecopus rohdei. cDNA sequencing revealed highly homologous regions (signal peptide and acidic region). Mature antioxidin-I has a novel primary sequence with low similarity compared with previously described amphibian's AOPs. Antioxidin-I adopts a random structure even at high concentrations of hydrophobic solvent, it has poor antimicrobial activity and poor performance in free radical scavenging assays in vitro, with the exception of the ORAC assay. However, antioxidin-I presented a low cytotoxicity and suppressed menadione-induced redox imbalance when tested with fibroblast in culture. In addition, it had the capacity to substantially attenuate the hypoxia-induced production of reactive oxygen species when tested in hypoxia exposed living microglial cells, suggesting a potential neuroprotective role for this peptide.
- Turning a Collagenesis-Inducing Peptide Into a Potent Antibacterial and Antibiofilm Agent Against Multidrug-Resistant Gram-Negative BacteriaPublication . Gomes, Ana; Bessa, Lucinda J.; Fernandes, Iva; Ferraz, Ricardo; Mateus, Nuno; Gameiro, Paula; Teixeira, Cátia; Gomes, PaulaAntimicrobial resistance is becoming one the most serious health threats worldwide, as it not only hampers effective treatment of infectious diseases using current antibiotics, but also increases the risks of medical procedures like surgery, transplantation, bone and dental implantation, chemotherapy, or chronic wound management. To date, there are no effective measures to tackle life-threatening nosocomial infections caused by multidrug resistant bacterial species, of which Gram-negative species within the so-called "ESKAPE" pathogens are the most worrisome. Many such bacteria are frequently isolated from severely infected skin lesions such as diabetic foot ulcers (DFU). In this connection, we are pursuing new peptide constructs encompassing antimicrobial and collagenesis-inducing motifs, to tackle skin and soft tissue infections by exerting a dual effect: antimicrobial protection and faster healing of the wound. This produced peptide 3.1-PP4 showed MIC values as low as 1.0 and 2.1 μM against Escherichia coli and Pseudomonas aeruginosa, respectively, and low toxicity to HFF-1 human fibroblasts. Remarkably, the peptide was also potent against multidrug-resistant isolates of Klebsiella pneumoniae, E. coli, and P. aeruginosa (MIC values between 0.5 and 4.1 μM), and hampered the formation of/disaggregated K. pneumoniae biofilms of resistant clinical isolates. Moreover, this notable hybrid peptide retained the collagenesis-inducing behavior of the reference cosmeceutical peptide C16-PP4 ("Matrixyl"). In conclusion, 3.1-PP4 is a highly promising lead toward development of a topical treatment for severely infected skin injuries.