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Antibiotics
Volume 9
Issue 12
10.3390/antibiotics9120840
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Article

Antibacterial and Anti-Inflammatory Activity of an Antimicrobial Peptide Synthesized with D Amino Acids

by
Jlenia Brunetti
1,*,†,
Veronica Carnicelli
2,†,
Alessia Ponzi
2,
Antonio Di Giulio
2,
Anna Rita Lizzi
2,
Loredana Cristiano
3,
Laura Cresti
4,
Giovanni Cappello
1,
Simona Pollini
5,6,
Lara Mosconi
5,
Gian Maria Rossolini
5,6,
Luisa Bracci
1,7,
Chiara Falciani
1 and
Alessandro Pini
1,7
1
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
2
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
3
Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
4
SetLance srl, Toscana Life Sciences, 53100 Siena, Italy
5
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
6
Microbiology and Virology Unit, Careggi University Hospital, 50134 Florence, Italy
7
Laboratory of Clinical Pathology, Santa Maria alle Scotte Hospital, 53100 Siena, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally.
Antibiotics 2020, 9(12), 840; https://doi.org/10.3390/antibiotics9120840
Submission received: 21 October 2020 / Revised: 17 November 2020 / Accepted: 22 November 2020 / Published: 24 November 2020
(This article belongs to the Special Issue Small Antimicrobial Peptides against Inflammation)
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Abstract

The peptide SET-M33 is a molecule synthesized in tetra-branched form which is being developed as a new antibiotic against Gram-negative bacteria. Its isomeric form with D amino acids instead of the L version (SET-M33D) is also able to kill Gram-positive bacteria because of its higher resistance to bacterial proteases (Falciani et al., PLoS ONE, 2012, 7, e46259). Here we report the strong in vitro activity of SET-M33D (MIC range 0.7–6.0 µM) against multiresistant pathogens of clinical interest, including Gram-positives Staphylococcus aureus, Staphylococcus saprophyticus, and Enterococcus faecalis, and various Gram-negative enterobacteriaceae. SET-M33D antibacterial activity is also confirmed in vivo against a MRSA strain of S. aureus with doses perfectly compatible with clinical use (5 and 2.5 mg/Kg). Moreover, SET-M33D strongly neutralized lipopolysaccharide (LPS) and lipoteichoic acid (LTA), thus exerting a strong anti-inflammatory effect, reducing expression of cytokines, enzymes, and transcription factors (TNF-α, IL6, COX-2, KC, MIP-1, IP10, iNOS, NF-κB) involved in the onset and evolution of the inflammatory process. These results, along with in vitro and in vivo toxicity data and the low frequency of resistance selection reported here, make SET-M33D a strong candidate for the development of a new broad spectrum antibiotic.
Keywords: anti-inflammatory activity; antibacterial agents; antimicrobial peptides anti-inflammatory activity; antibacterial agents; antimicrobial peptides

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MDPI and ACS Style

Brunetti, J.; Carnicelli, V.; Ponzi, A.; Di Giulio, A.; Lizzi, A.R.; Cristiano, L.; Cresti, L.; Cappello, G.; Pollini, S.; Mosconi, L.; et al. Antibacterial and Anti-Inflammatory Activity of an Antimicrobial Peptide Synthesized with D Amino Acids. Antibiotics 2020, 9, 840. https://doi.org/10.3390/antibiotics9120840

AMA Style

Brunetti J, Carnicelli V, Ponzi A, Di Giulio A, Lizzi AR, Cristiano L, Cresti L, Cappello G, Pollini S, Mosconi L, et al. Antibacterial and Anti-Inflammatory Activity of an Antimicrobial Peptide Synthesized with D Amino Acids. Antibiotics. 2020; 9(12):840. https://doi.org/10.3390/antibiotics9120840

Chicago/Turabian Style

Brunetti, Jlenia, Veronica Carnicelli, Alessia Ponzi, Antonio Di Giulio, Anna Rita Lizzi, Loredana Cristiano, Laura Cresti, Giovanni Cappello, Simona Pollini, Lara Mosconi, and et al. 2020. "Antibacterial and Anti-Inflammatory Activity of an Antimicrobial Peptide Synthesized with D Amino Acids" Antibiotics 9, no. 12: 840. https://doi.org/10.3390/antibiotics9120840

APA Style

Brunetti, J., Carnicelli, V., Ponzi, A., Di Giulio, A., Lizzi, A. R., Cristiano, L., Cresti, L., Cappello, G., Pollini, S., Mosconi, L., Rossolini, G. M., Bracci, L., Falciani, C., & Pini, A. (2020). Antibacterial and Anti-Inflammatory Activity of an Antimicrobial Peptide Synthesized with D Amino Acids. Antibiotics, 9(12), 840. https://doi.org/10.3390/antibiotics9120840

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