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Dr. Floriana Cappiello
Department of Biochemical Sciences, Sapienza University of Rome

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0 Antibiotic Resistance
0 Cell Lines
0 ELISA
0 Wound Healing
0 keratinocytes

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Journal article
Published: 08 January 2021 in International Journal of Molecular Sciences
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Persistent infections, such as those provoked by the Gram-negative bacterium Pseudomonas aeruginosa in the lungs of cystic fibrosis (CF) patients, can induce inflammation with lung tissue damage and progressive alteration of respiratory function. Therefore, compounds having both antimicrobial and immunomodulatory activities are certainly of great advantage in fighting infectious diseases and chronic inflammation. We recently demonstrated the potent antipseudomonal efficacy of the antimicrobial peptide (AMP) Esc(1-21) and its diastereomer Esc(1-21)-1c, namely Esc peptides. Here, we confirmed this antimicrobial activity by reporting on the peptides’ ability to kill P. aeruginosa once internalized into alveolar epithelial cells. Furthermore, by means of enzyme-linked immunosorbent assay and Western blot analyses, we investigated the peptides’ ability to detoxify the bacterial lipopolysaccharide (LPS) by studying their effects on the secretion of the pro-inflammatory cytokine IL-6 as well as on the expression of cyclooxygenase-2 from macrophages activated by P. aeruginosa LPS. In addition, by a modified scratch assay we showed that both AMPs are able to stimulate the closure of a gap produced in alveolar epithelial cells when cell migration is inhibited by concentrations of Pseudomonas LPS that mimic lung infection conditions, suggesting a peptide-induced airway wound repair. Overall, these results have highlighted the two Esc peptides as valuable candidates for the development of new multifunctional therapeutics for treatment of chronic infectious disease and inflammation, as found in CF patients.

ACS Style

Floriana Cappiello; Veronica Carnicelli; Bruno Casciaro; Maria Luisa Mangoni. Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation. International Journal of Molecular Sciences 2021, 22, 557 .

AMA Style

Floriana Cappiello, Veronica Carnicelli, Bruno Casciaro, Maria Luisa Mangoni. Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation. International Journal of Molecular Sciences. 2021; 22 (2):557.

Chicago/Turabian Style

Floriana Cappiello; Veronica Carnicelli; Bruno Casciaro; Maria Luisa Mangoni. 2021. "Antipseudomonal and Immunomodulatory Properties of Esc Peptides: Promising Features for Treatment of Chronic Infectious Diseases and Inflammation." International Journal of Molecular Sciences 22, no. 2: 557.

Journal article
Published: 10 December 2020 in International Journal of Molecular Sciences
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Bacterial biofilms are a serious threat for human health, and the Gram-positive bacterium Staphylococcus aureus is one of the microorganisms that can easily switch from a planktonic to a sessile lifestyle, providing protection from a large variety of adverse environmental conditions. Dormant non-dividing cells with low metabolic activity, named persisters, are tolerant to antibiotic treatment and are the principal cause of recalcitrant and resistant infections, including skin infections. Antimicrobial peptides (AMPs) hold promise as new anti-infective agents to treat such infections. Here for the first time, we investigated the activity of the frog-skin AMP temporin G (TG) against preformed S. aureus biofilm including persisters, as well as its efficacy in combination with tobramycin, in inhibiting S. aureus growth. TG was found to provoke ~50 to 100% reduction of biofilm viability in the concentration range from 12.5 to 100 µM vs ATCC and clinical isolates and to be active against persister cells (about 70–80% killing at 50–100 µM). Notably, sub-inhibitory concentrations of TG in combination with tobramycin were able to significantly reduce S. aureus growth, potentiating the antibiotic power. No critical cytotoxicity was detected when TG was tested in vitro up to 100 µM against human keratinocytes, confirming its safety profile for the development of a new potential anti-infective drug, especially for treatment of bacterial skin infections.

ACS Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Guendalina Fabiano; Luisa Torrini; Maria Luisa Mangoni. The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy against Staphylococcus aureus. International Journal of Molecular Sciences 2020, 21, 9410 .

AMA Style

Bruno Casciaro, Maria Rosa Loffredo, Floriana Cappiello, Guendalina Fabiano, Luisa Torrini, Maria Luisa Mangoni. The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy against Staphylococcus aureus. International Journal of Molecular Sciences. 2020; 21 (24):9410.

Chicago/Turabian Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Guendalina Fabiano; Luisa Torrini; Maria Luisa Mangoni. 2020. "The Antimicrobial Peptide Temporin G: Anti-Biofilm, Anti-Persister Activities, and Potentiator Effect of Tobramycin Efficacy against Staphylococcus aureus." International Journal of Molecular Sciences 21, no. 24: 9410.

Review
Published: 09 August 2020 in Molecules
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Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials.

ACS Style

Bruno Casciaro; Laura Mangiardi; Floriana Cappiello; Isabella Romeo; Maria Rosa Loffredo; Antonia Iazzetti; Andrea Calcaterra; Antonella Goggiamani; Francesca Ghirga; Maria Luisa Mangoni; Bruno Botta; Deborah Quaglio. Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections. Molecules 2020, 25, 3619 .

AMA Style

Bruno Casciaro, Laura Mangiardi, Floriana Cappiello, Isabella Romeo, Maria Rosa Loffredo, Antonia Iazzetti, Andrea Calcaterra, Antonella Goggiamani, Francesca Ghirga, Maria Luisa Mangoni, Bruno Botta, Deborah Quaglio. Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections. Molecules. 2020; 25 (16):3619.

Chicago/Turabian Style

Bruno Casciaro; Laura Mangiardi; Floriana Cappiello; Isabella Romeo; Maria Rosa Loffredo; Antonia Iazzetti; Andrea Calcaterra; Antonella Goggiamani; Francesca Ghirga; Maria Luisa Mangoni; Bruno Botta; Deborah Quaglio. 2020. "Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections." Molecules 25, no. 16: 3619.

Journal article
Published: 26 July 2020 in Antibiotics
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Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4–8 and 0.125–0.25 µM, respectively, along with a non-toxic profile after a short- and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor.

ACS Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Walter Verrusio; Vito Domenico Corleto; Maria Luisa Mangoni. Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities. Antibiotics 2020, 9, 448 .

AMA Style

Bruno Casciaro, Maria Rosa Loffredo, Floriana Cappiello, Walter Verrusio, Vito Domenico Corleto, Maria Luisa Mangoni. Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities. Antibiotics. 2020; 9 (8):448.

Chicago/Turabian Style

Bruno Casciaro; Maria Rosa Loffredo; Floriana Cappiello; Walter Verrusio; Vito Domenico Corleto; Maria Luisa Mangoni. 2020. "Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities." Antibiotics 9, no. 8: 448.

Review
Published: 13 June 2020 in Antibiotics
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The discovery of antibiotics has revolutionized the medicine and treatment of microbial infections. However, the current scenario has highlighted the difficulties in marketing new antibiotics and an exponential increase in the appearance of resistant strains. On the other hand, research in the field of drug-discovery has revaluated the potential of natural products as a unique source for new biologically active molecules and scaffolds for the medicinal chemistry. In this review, we first contextualized the worldwide problem of antibiotic resistance and the importance that natural products of plant origin acquire as a source of new lead compounds. We then focused on terpenes and their potential development as antimicrobials, highlighting those studies that showed an activity against conventional antibiotic-resistant strains.

ACS Style

Floriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga. The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections. Antibiotics 2020, 9, 1 .

AMA Style

Floriana Cappiello, Maria Rosa Loffredo, Cristina Del Plato, Silvia Cammarone, Bruno Casciaro, Deborah Quaglio, Maria Luisa Mangoni, Bruno Botta, Francesca Ghirga. The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections. Antibiotics. 2020; 9 (6):1.

Chicago/Turabian Style

Floriana Cappiello; Maria Rosa Loffredo; Cristina Del Plato; Silvia Cammarone; Bruno Casciaro; Deborah Quaglio; Maria Luisa Mangoni; Bruno Botta; Francesca Ghirga. 2020. "The Revaluation of Plant-Derived Terpenes to Fight Antibiotic-Resistant Infections." Antibiotics 9, no. 6: 1.

Journal article
Published: 01 September 2019 in Toxins
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Staphylococcus aureus is a major human pathogen causing a wide range of nosocomial infections including pulmonary, urinary, and skin infections. Notably, the emergence of bacterial strains resistant to conventional antibiotics has prompted researchers to find new compounds capable of killing these pathogens. Nature is undoubtedly an invaluable source of bioactive molecules characterized by an ample chemical diversity. They can act as unique platform providing new scaffolds for further chemical modifications in order to obtain compounds with optimized biological activity. A class of natural compounds with a variety of biological activities is represented by alkaloids, important secondary metabolites produced by a large number of organisms including bacteria, fungi, plants, and animals. In this work, starting from the screening of 39 alkaloids retrieved from a unique in-house library, we identified a heterodimer β-carboline alkaloid, nigritanine, with a potent anti-Staphylococcus action. Nigritanine, isolated from Strychnos nigritana, was characterized for its antimicrobial activity against a reference and three clinical isolates of S. aureus. Its potential cytotoxicity was also evaluated at short and long term against mammalian red blood cells and human keratinocytes, respectively. Nigritanine showed a remarkable antimicrobial activity (minimum inhibitory concentration of 128 µM) without being toxic in vitro to both tested cells. The analysis of the antibacterial activity related to the nigritanine scaffold furnished new insights in the structure–activity relationships (SARs) of β-carboline, confirming that dimerization improves its antibacterial activity. Taking into account these interesting results, nigritanine can be considered as a promising candidate for the development of new antimicrobial molecules for the treatment of S. aureus-induced infections.

ACS Style

Bruno Casciaro; Andrea Calcaterra; Floriana Cappiello; Mattia Mori; Maria Loffredo; Francesca Ghirga; Maria Mangoni; Bruno Botta; Deborah Quaglio. Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections. Toxins 2019, 11, 511 .

AMA Style

Bruno Casciaro, Andrea Calcaterra, Floriana Cappiello, Mattia Mori, Maria Loffredo, Francesca Ghirga, Maria Mangoni, Bruno Botta, Deborah Quaglio. Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections. Toxins. 2019; 11 (9):511.

Chicago/Turabian Style

Bruno Casciaro; Andrea Calcaterra; Floriana Cappiello; Mattia Mori; Maria Loffredo; Francesca Ghirga; Maria Mangoni; Bruno Botta; Deborah Quaglio. 2019. "Nigritanine as a New Potential Antimicrobial Alkaloid for the Treatment of Staphylococcus aureus-Induced Infections." Toxins 11, no. 9: 511.