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Pharmaceuticals
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Natural Anti-Biofilm Agents
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Natural Anti-Biofilm Agents

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (20 March 2024) | Viewed by 11698

Special Issue Editors

Dr. Margherita Cacaci

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Guest Editor
Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics Università Cattolica del Sacro Cuore, Rome, Italy
Interests: antimicrobial resistance; new antimicrobial compounds; biofilm; biofilm-related infections; anti-biofilm; nanomaterials; mycology; advanced diagnostic
Dr. Riccardo Torelli

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Guest Editor
Department of Laboratory and Infectious Disease Sciences, "A. Gemelli" University Hospital Foundation IRCCS, Rome, Italy
Interests: clinical mycology; antimicrobial resistance; antimicrobial compounds; biofilm-related infections; anti-biofilm nanomaterials

Special Issue Information

Dear Colleagues,

Biofilm is a complex structure composed of an organized aggregation of single or multiple microbial species, which is surrounded by an extra-cellular polymeric substance and attached to biotic or abiotic surfaces. Cells in biofilm are more resistant to environmental stresses such as nutrient depletion. Biofilm can be formed in the human body or medical devices, causing difficult-to-treat infections with a high risk of recalcitrant episodes. This is due to the different properties of the biofilm: evasion from the immune system, low metabolic rate, tolerance, and resistance to antimicrobial therapies. Research in recent years has aimed to identify new compounds with anti-biofilm activity; particularly, the use of “green” molecules, such as phytochemicals, antimicrobial peptides, green synthetized nanoparticles and nanomaterials, are of great interest. The scope of this Special Issue is to publish papers about the anti-biofilm activity of green compounds and their possible application in medicine, the food industry and livestock. Submitted manuscripts should include in vitro and/or in vivo studies of phytochemicals (phenolics, essential oils, terpenoids, lectins, alkaloids, polypeptides and polyacetylenes); antimicrobial peptides; naturally synthetized nanoparticles (silver nanoparticles, cooper, titanium, etc.); and green synthetized nanomaterials that are able to inhibit a microorganism’s adhesion and biofilm formation, along with their mechanism of action and/or possible application.

Dr. Margherita Cacaci
Dr. Riccardo Torelli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biofilm
  • drug-resistance
  • green anti-biofilm antimicrobial peptides
  • phytochemicals
  • new green nanomaterials for medical devices or animal food contact surfaces

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Published Papers (6 papers)

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Research

15 pages, 728 KiB  
Article
Exploring the Antibiofilm Effect of Sertraline in Synergy with Cinnamomum verum Essential Oil to Counteract Candida Species
by Alexia Barbarossa, Antonio Rosato, Antonio Carrieri, Luciana Fumarola, Roberta Tardugno, Filomena Corbo, Giuseppe Fracchiolla and Alessia Carocci
Pharmaceuticals 2024, 17(9), 1109; https://doi.org/10.3390/ph17091109 - 23 Aug 2024
Viewed by 830
Abstract
The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming [...] Read more.
The emergence and spread of drug-resistant pathogens, resulting in antimicrobial resistance, continue to compromise our capability to handle commonly occurring infectious diseases. The rapid global spread of multi-drug-resistant pathogens, particularly systemic fungal infections, presents a significant concern, as existing antimicrobial drugs are becoming ineffective against them. In recent decades, there has been a notable increase in systemic fungal infections, primarily caused by Candida species, which are progressively developing resistance to azoles. Moreover, Candida species biofilms are among the most common in clinical settings. In particular, they adhere to biomedical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. In recent years, many research programs have concentrated on the development of novel compounds with possible antimicrobial effects to address this issue, and new sources, such as plant-derived antimicrobial compounds, have been thoroughly investigated. Essential oils (EOs), among their numerous pharmacological properties, exhibit antifungal, antibacterial, and antiviral activities and have been examined at a global scale as the possible origin of novel antimicrobial compounds. A recent work carried out by our research group concerned the synergistic antibacterial activities of commercially available and chemically characterized Cinnamomum verum L. essential oil (C. verum EO) in association with sertraline, a selective serotonin reuptake inhibitor whose repositioning as a non-antibiotic drug has been explored over the years with encouraging results. The aim of this work was to explore the synergistic effects of C. verum EO with sertraline on both planktonic and sessile Candida species cells. Susceptibility testing and testing of the synergism of sertraline and C. verum EO against planktonic and sessile cells were performed using a broth microdilution assay and checkerboard methods. A synergistic effect was evident in both the planktonic cells and mature biofilms, with significant reductions in fungal viability. Indeed, the fractional inhibitory concentration index (FICI) was lower than 0.5 for all the associations, thus indicating significant synergism of the associations with the Candida strains examined. Moreover, the concentrations of sertraline able to inhibit Candida spp. strain growth and biofilm formation significantly decreased when it was used in combination with C. verum EO for all the strains considered, with a reduction percentage in the amount of each associated component ranging from 87.5% to 97%. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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11 pages, 1023 KiB  
Article
Evaluating the Effectiveness of Phellodendron Amurense Ruprecht Extract as a Natural Anti-Caries Material
by Yu-Rin Kim, Gyoo-Cheon Kim and Seoul-Hee Nam
Pharmaceuticals 2024, 17(5), 603; https://doi.org/10.3390/ph17050603 - 8 May 2024
Viewed by 966
Abstract
Background: This study aimed to investigate the antibacterial and cytotoxic potential of Phellodendron amurense Ruprecht (PAR) extract against Streptococcus mutans (S. mutans) and explore the possibility of using PAR extract as an anticariogenic agent. Methods: Mixed extracts were prepared at 0, [...] Read more.
Background: This study aimed to investigate the antibacterial and cytotoxic potential of Phellodendron amurense Ruprecht (PAR) extract against Streptococcus mutans (S. mutans) and explore the possibility of using PAR extract as an anticariogenic agent. Methods: Mixed extracts were prepared at 0, 1.25, 2.5, and 5 mg/mL concentrations, and an S. mutans-containing solution of 100 μL was inoculated into the medium. The survival rate of human keratinocyte (HaCaT) cells was assessed to confirm stability. One-way ANOVA was performed to evaluate the antibacterial activity against S. mutans and the proliferation of HaCaT cells. Results: Higher concentrations of the PAR extract showed more growth inhibition of S. mutans over time, with the complete inactivation of S. mutans at 5 mg/mL. HaCaT cell density was reduced at a PAR extract concentration of 1.25 mg/mL, but IC50 was not observed, confirming that the concentration used did not affect the cytotoxicity and proliferation. Conclusions: Results showed that the PAR extract was excellent as a natural substance with anticariogenic effects that inhibited the growth of S. mutans and did not affect the cell viability, thus indicating the potential for clinical application. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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22 pages, 3573 KiB  
Article
Effect of Matricaria aurea Essential Oils on Biofilm Development, Virulence Factors and Quorum Sensing-Dependent Genes of Pseudomonas aeruginosa
by Haitham Qaralleh, Sultan Ayesh Mohammed Saghir, Muhamad O. Al-limoun, Saif M. Dmor, Khaled Khleifat, Basma Ezzat Mustafa Al-Ahmad, Laila Al-Omari, Yasser Tabana, Ramzi A. Mothana, Hanan M. Al-Yousef and Abdulaziz M. Alqahtani
Pharmaceuticals 2024, 17(3), 386; https://doi.org/10.3390/ph17030386 - 18 Mar 2024
Cited by 1 | Viewed by 1902
Abstract
The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils [...] Read more.
The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils (EO), to combat bacterial pathogenicity. The primary aim of this research was to analyze the chemical composition of the aerial part of the Matricaria aurea (M. aureas) EO and evaluate its potential for inhibiting quorum sensing (QS) and disrupting biofilm formation in Pseudomonas aeruginosa (P. aeruginosa). The gas chromatography-mass spectrometry (GCMS) analysis unveiled that α-bisabolol oxide A constituted the predominant portion, comprising 64.8% of the total, with β-bisabolene at 6.3% and α-farnesene at 4.8% following closely behind. The antibiofilm efficacy was observed at concentrations of 0.3, 0.15, and 0.08 mg/mL, demonstrating negligible effects on cell viability. Furthermore, the EO from M. aurea effectively inhibited the formation of P. aeruginosa biofilms by diminishing aggregation, hydrophobicity, and swarming motility. Significantly, the EO treatment resulted in a conspicuous decrease in the production of pyocyanin, rhamnolipid, and extracellular polymeric substances (EPS), along with a reduction in the enzymatic activity of protease and chitinase. The EO effectively hindered QS by disrupting QS mechanisms, resulting in a marked decline in the secretion of N-Acyl homoserine lactone (AHL) molecules and the expression of phazA1 and aprA genes. This investigation offers compelling evidence supporting the potential of M. aurea EO as a promising therapeutic candidate for addressing infectious diseases induced by biofilm formation. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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24 pages, 5364 KiB  
Article
Polyglactin 910 Meshes Coated with Sustained-Release Cannabigerol Varnish Inhibit Staphylococcus aureus Biofilm Formation and Macrophage Cytokine Secretion: An In Vitro Study
by Mustafa Abudalu, Muna Aqawi, Ronit Vogt Sionov, Michael Friedman, Irith Gati, Yaron Munz, Gil Ohana and Doron Steinberg
Pharmaceuticals 2023, 16(5), 745; https://doi.org/10.3390/ph16050745 - 13 May 2023
Viewed by 2094
Abstract
Synthetic surgical meshes are commonly used in abdominal wall reconstruction surgeries to strengthen a weak abdominal wall. Common mesh-related complications include local infection and inflammatory processes. Because cannabigerol (CBG) has both antibacterial and anti-inflammatory properties, we proposed that coating VICRYL (polyglactin 910) mesh [...] Read more.
Synthetic surgical meshes are commonly used in abdominal wall reconstruction surgeries to strengthen a weak abdominal wall. Common mesh-related complications include local infection and inflammatory processes. Because cannabigerol (CBG) has both antibacterial and anti-inflammatory properties, we proposed that coating VICRYL (polyglactin 910) mesh with a sustained-release varnish (SRV) containing CBG would prevent these complications. We used an in vitro infection model with Staphylococcus aureus and an in vitro inflammation model of lipopolysaccharide (LPS)-stimulated macrophages. Meshes coated with either SRV-placebo or SRV-CBG were exposed daily to S. aureus in tryptic soy medium (TSB) or macrophage Dulbecco’s modified eagle medium (DMEM). Bacterial growth and biofilm formation in the environment and on the meshes were assessed by changes in optical density, bacterial ATP content, metabolic activity, crystal violet staining, spinning disk confocal microscopy (SDCM), and high-resolution scanning electron microscopy (HR-SEM). The anti-inflammatory effect of the culture medium that was exposed daily to the coated meshes was analyzed by measuring the release of the cytokines IL-6 and IL-10 from LPS-stimulated RAW 264.7 macrophages with appropriate ELISA kits. Additionally, a cytotoxicity assay was performed on Vero epithelial cell lines. We observed that compared with SRV-placebo, the segments coated with SRV-CBG inhibited the bacterial growth of S. aureus in the mesh environment for 9 days by 86 ± 4% and prevented biofilm formation and metabolic activity in the surroundings for 9 days, with respective 70 ± 2% and 95 ± 0.2% reductions. The culture medium that was incubated with the SRV-CBG-coated mesh inhibited LPS-induced secretion of IL-6 and IL-10 from the RAW 264.7 macrophages for up to 6 days without affecting macrophage viability. A partial anti-inflammatory effect was also observed with SRV-placebo. The conditioned culture medium was not toxic to Vero epithelial cells, which had an IC50 of 25 µg/mL for CBG. In conclusion, our data indicate a potential role of coating VICRYL mesh with SRV-CBG in preventing infection and inflammation in the initial period after surgery. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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17 pages, 7178 KiB  
Article
Effects of Piper betle Extracts against Biofilm Formation by Methicillin-Resistant Staphylococcus pseudintermedius Isolated from Dogs
by Arpron Leesombun, Sivapong Sungpradit, Norasuthi Bangphoomi, Orathai Thongjuy, Jantraporn Wechusdorn, Sunee Riengvirodkij, Jakaphan Wannawong and Sookruetai Boonmasawai
Pharmaceuticals 2023, 16(5), 741; https://doi.org/10.3390/ph16050741 - 12 May 2023
Cited by 1 | Viewed by 2368
Abstract
Emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolated from dogs with cutaneous and wound infections has significantly impacted veterinary medicine. This study aimed to isolate S. pseudintermedius from canine pyoderma and investigate the effects of ethanolic extracts of Piper betle (PB), P. sarmentosum (PS), [...] Read more.
Emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolated from dogs with cutaneous and wound infections has significantly impacted veterinary medicine. This study aimed to isolate S. pseudintermedius from canine pyoderma and investigate the effects of ethanolic extracts of Piper betle (PB), P. sarmentosum (PS), and P. nigrum (PN) on the bacterial growth and biofilm formation of S. pseudintermedius and MRSP. Of the isolated 152 isolates, 53 were identified as S. pseudintermedius using polymerase chain reaction, and 10 isolates (6.58%) were identified as MRSP based on the presence of mecA. Based on phenotype, 90% of MRSPs were multidrug-resistant. All MRSP had moderate (10%, 1/10) and strong (90%, 9/10) biofilm production ability. PB extracts were the most effective in inhibiting planktonic cells, and the minimum inhibitory concentration at which ≥50% of the isolates were inhibited (MIC50) was 256 µg/mL (256–1024 µg/mL) for S. pseudintermedius isolates and 512 µg/mL (256–1024 µg/mL) for MRSP isolates. The MIC90 for S. pseudintermedius and MRSP was 512 µg/mL. In XTT assay, PB at 4× MIC showed an inhibition rate of 39.66–68.90% and 45.58–59.13% for S. pseudintermedius and MRSP, respectively, in inhibiting biofilm formation. For PB at 8× MIC, the inhibition rates for S. pseudintermedius and MRSP were 50.74–81.66% and 59.57–78.33%, respectively. Further, 18 compounds were identified in PB using gas chromatography–mass spectrometry, and hydroxychavicol (36.02%) was the major constituent. These results indicated that PB could inhibit bacteria growth of and biofilm formation by S. pseudintermedius and MRSP isolated from canine pyoderma in a concentration-dependent manner. Therefore, PB is a potential candidate for the treatment of MRSP infection and biofilm formation in veterinary medicine. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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17 pages, 4777 KiB  
Article
Curcumin-Functionalized Graphene Oxide Strongly Prevents Candida parapsilosis Adhesion and Biofilm Formation
by Margherita Cacaci, Damiano Squitieri, Valentina Palmieri, Riccardo Torelli, Giordano Perini, Michela Campolo, Maura Di Vito, Massimiliano Papi, Brunella Posteraro, Maurizio Sanguinetti and Francesca Bugli
Pharmaceuticals 2023, 16(2), 275; https://doi.org/10.3390/ph16020275 - 11 Feb 2023
Cited by 10 | Viewed by 2683
Abstract
Candida parapsilosis is the major non-C. albicans species involved in the colonization of central venous catheters, causing bloodstream infections. Biofilm formation on medical devices is considered one of the main causes of healthcare-associated infections and represents a global public health problem. In [...] Read more.
Candida parapsilosis is the major non-C. albicans species involved in the colonization of central venous catheters, causing bloodstream infections. Biofilm formation on medical devices is considered one of the main causes of healthcare-associated infections and represents a global public health problem. In this context, the development of new nanomaterials that exhibit anti-adhesive and anti-biofilm properties for the coating of medical devices is crucial. In this work, we aimed to characterize the antimicrobial activity of two different coated-surfaces, graphene oxide (GO) and curcumin-graphene oxide (GO/CU) for the first time, against C. parapsilosis. We report the capacity of GO to bind and stabilize CU molecules, realizing a homogenous coated surface. We tested the anti-planktonic activity of GO and GO/CU by growth curve analysis and quantification of Reactive Oxigen Species( ROS) production. Then, we tested the antibiofilm activity by adhesion assay, crystal violet assay, and live and dead assay; moreover, the inhibition of the formation of a mature biofilm was investigated by a viability test and the use of specific dyes for the visualization of the cells and the extra-polymeric substances. Our data report that GO/CU has anti-planktonic, anti-adhesive, and anti-biofilm properties, showing a 72% cell viability reduction and a decrease of 85% in the secretion of extra-cellular substances (EPS) after 72 h of incubation. In conclusion, we show that the GO/CU conjugate is a promising material for the development of medical devices that are refractory to microbial colonization, thus leading to a decrease in the impact of biofilm-related infections. Full article
(This article belongs to the Special Issue Natural Anti-Biofilm Agents)
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