Natural Products and Bio-Nanomaterials: Novel Strategies to Overcome Antibiotic Resistance

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Plant-Derived Antibiotics".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 26670

Special Issue Editors


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Guest Editor
Department of Microbiology, Universidade Estadual de Londrina, Londrina, Brazil
Interests: resistance; pharmacy; nanoparticles; bacterial control; in vivo model; resistance to antimicrobials
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Microbiology, Universidade Estadual de Londrina, Londrina, Brazil
Interests: nanotechnology

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Guest Editor
Department of Microbiology, Universidade Estadual de Londrina, Londrina, Brazil
Interests: product natural; antimicrobials

Special Issue Information

Dear Colleagues,

The emergence of superbugs is a concern in Public Health that accounts for millions of deaths in worldwide. Multidrug-resistant (MDR) microorganisms have increased in hospital environments and in communities, with high streaming rates. Conventional antimicrobials have not been effective enough in eliminating MDRs. So, new alternatives using natural products and nanoparticles can be interesting in infection control.

Natural products are a trend in biomedical applications as antimicrobials due to their low toxicity and environmental safety. Many different plants have been used as pharmaceuticals with benefits and advantages in infection control. However, this use alone presents some difficulties (cost, efficacy, seasonality, etc.) suggesting increments in their compounds.

Nanotechnology or Nanoscience is the study and application of small particles (between 1 and 100 nm) to produce new structures, material, and devices. This size and charge allow optimizing some physicochemical properties, as well as biological activities. Some nanomaterials with antimicrobial effects have been applied in the field of medicine with satisfactory results. These materials can adopt interesting strategies such as nanoencapsulation, compounds delivery, magnetic targeting and synergic associations. 

In this way, our Special Issue will receive articles focusing on the antimicrobial activity using natural products (from marine, plants, microorganisms, etc.) and bionanomaterials for prevention or therapy against pathogens, including MDRs. Authors can send original research or review approaching this theme.

Dr. Renata Katsuko Takayama Kobayashi
Dr. Gerson Nakazato
Dr. Sara Scandorieiro
Guest Editors

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Keywords

  • nanotechnology
  • material
  • antimicrobial
  • nature
  • resistance
  • nanoparticles
  • strategy

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Published Papers (9 papers)

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Research

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19 pages, 6612 KiB  
Article
From Burst to Sustained Release: The Effect of Antibiotic Structure Incorporated into Chitosan-Based Films
by Nathália F. Sczesny, Helton J. Wiggers, Cecilia Z. Bueno, Pascale Chevallier, Francesco Copes and Diego Mantovani
Antibiotics 2024, 13(11), 1055; https://doi.org/10.3390/antibiotics13111055 - 6 Nov 2024
Viewed by 1419
Abstract
Background/Objectives: Medical devices are susceptible to bacterial colonization and biofilm formation, which can result in severe infections, leading to prolonged hospital stays and increased burden on society. Antibacterial films have the potential to assist in preventing biofilm formation, thereby reducing administration of antibiotics [...] Read more.
Background/Objectives: Medical devices are susceptible to bacterial colonization and biofilm formation, which can result in severe infections, leading to prolonged hospital stays and increased burden on society. Antibacterial films have the potential to assist in preventing biofilm formation, thereby reducing administration of antibiotics and the emergence of antibiotic-resistant strains. In a previous study, a chitosan-based matrix crosslinked with tannic acid and loaded with gentamicin was reported. In this study, five different antibiotics (moxifloxacin, ciprofloxacin, trimethoprim, sulfamethoxazole or linezolid) were loaded into these chitosan-based films, and their impact on the release behavior carefully assessed. Methods: The samples were characterized according to their thickness, swelling, and mass loss in phosphate-buffered saline (PBS), as well as by morphology using scanning electron microscopy (SEM) and optical phase contrast microscopy. Antibiotic release over time was quantified in PBS by high-performance liquid chromatography (HPLC). Antibacterial activity was investigated by disk diffusion test and antibiotic release over time. Finally, the cytotoxicity of the samples was assessed with human dermal fibroblasts. Results: The obtained results differed significantly, especially regarding the antibiotic release time and antibacterial activity, which varied from one day to six months, enabling classification of the films from burst/transient to prolonged release. The films also showed antibacterial features against bacteria mostly present in medical devices and displayed to be non-cytotoxic. Conclusions: In conclusion, it was demonstrated that the antibiotics structure significantly alters the release kinetics, and that by carefully selecting the antibiotic, the consequent release can be tuned. This approach yielded films that could be used for potentially-scalable release in antimicrobial coatings specific to medical devices, aiming to reduce biomaterial associated infections (BAIs). Full article
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16 pages, 2956 KiB  
Article
In Vitro Virucidal Activity of Different Essential Oils against Bovine Viral Diarrhea Virus Used as Surrogate of Human Hepatitis C Virus
by Gianvito Lanave, Francesco Pellegrini, Francesco Triggiano, Osvalda De Giglio, Maria Stella Lucente, Georgia Diakoudi, Cristiana Catella, Arturo Gentile, Roberta Tardugno, Giuseppe Fracchiolla, Vito Martella and Michele Camero
Antibiotics 2024, 13(6), 514; https://doi.org/10.3390/antibiotics13060514 - 31 May 2024
Cited by 2 | Viewed by 1370
Abstract
The hepatitis C virus (HCV) is a major hepatotropic virus that affects humans with increased risk of developing hepatocellular carcinoma. The bovine viral diarrhea virus (BVDV) causes abortion, calf mortality and poor reproductive performance in cattle. Due the difficulties of in vitro cultivation [...] Read more.
The hepatitis C virus (HCV) is a major hepatotropic virus that affects humans with increased risk of developing hepatocellular carcinoma. The bovine viral diarrhea virus (BVDV) causes abortion, calf mortality and poor reproductive performance in cattle. Due the difficulties of in vitro cultivation for HCV, BVDV has been used as surrogate for in vitro assessment of the efficacy of antivirals. Essential oils (EOs) display antiviral and virucidal activity on several viral pathogens. In this study, the virucidal activity of five EOs, Salvia officinalis L. EO (SEO), Melissa officinalis L. EO (MEO), Citrus lemon EO (LEO), Rosmarinus officinalis L. EO (REO) and Thymus vulgaris L. EO (TEO) against BVDV was evaluated in vitro at different concentrations for several time contacts. MEO and LEO were able to considerably inactivate BVDV with a time- and dose-dependent fashion. MEO and LEO at the highest concentrations decreased viral titer by 2.00 and 2.25 log10 TCID50/50 μL at 8 h contact time, respectively. SEO, REO and TEO displayed mild virucidal activity at the highest concentrations for 8 h contact times. In this study, the virucidal efficacies of MEO and LEO against BVDV were observed regardless of compound concentration and contact time. Further studies are needed to confirm the potential use of MEO and LEO as surface disinfectants. Full article
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10 pages, 1101 KiB  
Article
Gum Arabic Increases Phagocytosis of Escherichia coli by Blood Leukocytes of Young and Old Healthy Volunteers
by Christin Freibrodt, Shima Baien, Maren von Köckritz-Blickwede, Nicole de Buhr, Roland Nau and Jana Seele
Antibiotics 2024, 13(6), 482; https://doi.org/10.3390/antibiotics13060482 - 24 May 2024
Viewed by 1273
Abstract
Background: Gum arabic, a polysaccharide exudate from Acacia senegal (L.) Willdenow trees, has already been used by African native people in natural medicine. Methods: Using whole-blood samples from young (20–35 years) and older (>80 years) healthy volunteers (each group n = 10), the [...] Read more.
Background: Gum arabic, a polysaccharide exudate from Acacia senegal (L.) Willdenow trees, has already been used by African native people in natural medicine. Methods: Using whole-blood samples from young (20–35 years) and older (>80 years) healthy volunteers (each group n = 10), the effect of an aqueous solution of GA on phagocytosis of Escherichia coli was examined with a gentamicin protection assay. Whole-blood samples of each volunteer were stimulated with GA and as a control with CpG oligodeoxynucleotides (Toll-like receptor -9 agonists) for 2 h, then co-incubated with E. coli for 30 min and thereafter treated with gentamicin for up to 240 min to kill extracellular bacteria. Then, whole-blood cells were lysed with distilled water, and colony-forming units were counted by quantitative plating. Cytokine enzyme-linked immunosorbent assay for the detection of TNF-α and IL-6 was performed using the blood supernatant. Results: The GA concentration tested (20 mg/mL) did not affect the viability of eukaryotic cells. Phagocytosis of E. coli by whole-blood leukocytes derived from young (p = 0.008) and older (p = 0.004) healthy volunteers was increased by 120.8% (young) and 39.2% (old) after stimulation with GA. In contrast, CpG only stimulated the bacterial phagocytosis by cells derived from young volunteers (p = 0.004). Stimulation of whole blood with GA increased the intracellular killing of E. coli in young (p = 0.045) and older volunteers (p = 0.008) and induced a TNF-α release in whole blood collected from older volunteers but not from younger ones (p = 0.008). Conclusions: These data encourage the isolation of active compounds of GA and the initiation of clinical trials addressing the preventive effect of GA on bacterial infections. Full article
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18 pages, 1036 KiB  
Article
Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems
by Anna Stasiłowicz-Krzemień, Daria Szymanowska, Piotr Szulc and Judyta Cielecka-Piontek
Antibiotics 2024, 13(4), 369; https://doi.org/10.3390/antibiotics13040369 - 17 Apr 2024
Cited by 3 | Viewed by 2965
Abstract
The compounds present in hemp show multidirectional biological activity. It is related to the presence of secondary metabolites, mainly cannabinoids, terpenes, and flavonoids, and the synergy of their biological activity. The aim of this study was to assess the activity of the Henola [...] Read more.
The compounds present in hemp show multidirectional biological activity. It is related to the presence of secondary metabolites, mainly cannabinoids, terpenes, and flavonoids, and the synergy of their biological activity. The aim of this study was to assess the activity of the Henola Cannabis sativae extract and its combinations with selected carriers (polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer, magnesium aluminometasilicate, and hydroxypropyl-β-cyclodextrin) in terms of antimicrobial, probiotic, and immunobiological effects. As a result of the conducted research, the antimicrobial activity of the extract was confirmed in relation to the following microorganisms: Clostridium difficile, Listeria monocytogenes, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus pyrogenes, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aereuginosa, and Candida albicans (microorganism count was reduced from ~102 CFU mL−1 to <10 CFU mL−1 in most cases). Additionally, for the system with hydroxypropyl-β-cyclodextrin, a significant probiotic potential against bacterial strains was established for strains Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus reuteri, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus fermentum, and Streptococcus thermophilus (microorganism count was increased from ~102 to 104–107). In terms of immunomodulatory properties, it was determined that the tested extract and the systems caused changes in IL-6, IL-8, and TNF-α levels. Full article
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17 pages, 2755 KiB  
Article
Cellulose Hydrogel with Hyaluronic Acid and Silver Nanoparticles: Sustained-Release Formulation with Antibacterial Properties against Pseudomonas aeruginosa
by Mirian Sumini, Clara Ruiz de Souza, Gabriel Jonathan Sousa Andrade, Igor Roberto Cabral Oliveira, Sara Scandorieiro, Cesar Augusto Tischer, Renata Katsuko Takayama Kobayashi and Gerson Nakazato
Antibiotics 2023, 12(5), 873; https://doi.org/10.3390/antibiotics12050873 - 8 May 2023
Cited by 5 | Viewed by 3321
Abstract
Pathogenic bacteria resistant to conventional antibiotics represent a global challenge and justify the need for new antimicrobials capable of combating bacterial multidrug resistance. This study describes the development of a topical hydrogel in a formulation composed of cellulose, hyaluronic acid (HA), and silver [...] Read more.
Pathogenic bacteria resistant to conventional antibiotics represent a global challenge and justify the need for new antimicrobials capable of combating bacterial multidrug resistance. This study describes the development of a topical hydrogel in a formulation composed of cellulose, hyaluronic acid (HA), and silver nanoparticles (AgNPs) against strains of Pseudomonas aeruginosa. AgNPs as an antimicrobial agent were synthesized by a new method based on green chemistry, using arginine as a reducing agent and potassium hydroxide as a carrier. Scanning electron microscopy showed the formation of a composite between cellulose and HA in a three-dimensional network of cellulose fibrils, with thickening of the fibrils and filling of spaces by HA with the presence of pores. Ultraviolet-visible spectroscopy (UV-vis) and particle size distribution for dynamic light scattering (DLS) confirmed the formation of AgNPs with peak absorption at ~430 nm and 57.88 nm. AgNPs dispersion showed a minimum inhibitory concentration (MIC) of 1.5 µg/mL. The time–kill assay showed that after 3 h of exposure to the hydrogel containing AgNPs, there were no viable cells, corresponding to a bactericidal efficacy of 99.999% in the 95% confidence level. We obtained a hydrogel that is easy to apply, with sustained release and bactericidal properties against strains of Pseudomonas aeruginosa at low concentrations of the agent. Full article
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20 pages, 4680 KiB  
Article
Synergistic Antifungal Interaction between Pseudomonas aeruginosa LV Strain Metabolites and Biogenic Silver Nanoparticles against Candida auris
by Laís Fernanda de Almeida Spoladori, Gabriella Maria Andriani, Isabela Madeira de Castro, Helena Tiemi Suzukawa, Ana Carolina Ramos Gimenes, Guilherme Bartolomeu-Gonçalves, Kelly Ishida, Gerson Nakazato, Phileno Pinge-Filho, Rayanne Regina Beltrame Machado, Celso Vataru Nakamura, Galdino Andrade, Eliandro Reis Tavares, Lucy Megumi Yamauchi and Sueli Fumie Yamada-Ogatta
Antibiotics 2023, 12(5), 861; https://doi.org/10.3390/antibiotics12050861 - 6 May 2023
Cited by 7 | Viewed by 2450
Abstract
Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form [...] Read more.
Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 μg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fungal cells. F4a and indolin-3-one combined with bioAgNP exhibited synergistic fungicidal activity against planktonic cells. F4a, alone or combined with bioAgNP, also caused a significant decrease in the number of viable cells within the biofilms. No cytotoxicity to mammalian cells was detected for bacterial metabolites combined with bioAgNP at synergistic concentrations that presented antifungal activity. These results indicate the potential of F4a combined with bioAgNP as a new strategy for controlling C. auris infections. Full article
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32 pages, 73558 KiB  
Article
Antibiofilm Effect of Biogenic Silver Nanoparticles Combined with Oregano Derivatives against Carbapenem-Resistant Klebsiella pneumoniae
by Sara Scandorieiro, Franciele Maira M. B. Teixeira, Mara C. L. Nogueira, Luciano A. Panagio, Admilton G. de Oliveira, Nelson Durán, Gerson Nakazato and Renata K. T. Kobayashi
Antibiotics 2023, 12(4), 756; https://doi.org/10.3390/antibiotics12040756 - 14 Apr 2023
Cited by 14 | Viewed by 3193
Abstract
Resistant bacteria may kill more people than COVID-19, so the development of new antibacterials is essential, especially against microbial biofilms that are reservoirs of resistant cells. Silver nanoparticles (bioAgNP), biogenically synthesized using Fusarium oxysporum, combined with oregano derivatives, present a strategic antibacterial [...] Read more.
Resistant bacteria may kill more people than COVID-19, so the development of new antibacterials is essential, especially against microbial biofilms that are reservoirs of resistant cells. Silver nanoparticles (bioAgNP), biogenically synthesized using Fusarium oxysporum, combined with oregano derivatives, present a strategic antibacterial mechanism and prevent the emergence of resistance against planktonic microorganisms. Antibiofilm activity of four binary combinations was tested against enteroaggregative Escherichia coli (EAEC) and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC): oregano essential oil (OEO) plus bioAgNP, carvacrol (Car) plus bioAgNP, thymol (Thy) plus bioAgNP, and Car plus Thy. The antibiofilm effect was accessed using crystal violet, MTT, scanning electron microscopy, and Chromobacterium violaceum anti-quorum-sensing assays. All binary combinations acted against preformed biofilm and prevented its formation; they showed improved antibiofilm activity compared to antimicrobials individually by reducing sessile minimal inhibitory concentration up to 87.5% or further decreasing biofilm metabolic activity and total biomass. Thy plus bioAgNP extensively inhibited the growth of biofilm in polystyrene and glass surfaces, disrupted three-dimensional biofilm structure, and quorum-sensing inhibition may be involved in its antibiofilm activity. For the first time, it is shown that bioAgNP combined with oregano has antibiofilm effect against bacteria for which antimicrobials are urgently needed, such as KPC. Full article
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Review

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36 pages, 3954 KiB  
Review
Antimicrobial Action Mechanisms of Natural Compounds Isolated from Endophytic Microorganisms
by Farkhod Eshboev, Nilufar Mamadalieva, Pavel A. Nazarov, Hidayat Hussain, Vladimir Katanaev, Dilfuza Egamberdieva and Shakhnoz Azimova
Antibiotics 2024, 13(3), 271; https://doi.org/10.3390/antibiotics13030271 - 18 Mar 2024
Cited by 14 | Viewed by 6894
Abstract
Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as [...] Read more.
Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites. Full article
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Other

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30 pages, 2704 KiB  
Systematic Review
Cannabinoids as Antibacterial Agents: A Systematic and Critical Review of In Vitro Efficacy Against Streptococcus and Staphylococcus
by Dhakshila Niyangoda, Myat Lin Aung, Mallique Qader, Wubshet Tesfaye, Mary Bushell, Fabian Chiong, Danny Tsai, Danish Ahmad, Indira Samarawickrema, Mahipal Sinnollareddy and Jackson Thomas
Antibiotics 2024, 13(11), 1023; https://doi.org/10.3390/antibiotics13111023 - 30 Oct 2024
Cited by 1 | Viewed by 2495
Abstract
Background: Two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, are becoming increasingly antibiotic-resistant. Despite the urgency, only a few new antibiotics have been approved to address these infections. Although cannabinoids have been noted for their antibacterial properties, a comprehensive review of [...] Read more.
Background: Two major bacterial pathogens, Staphylococcus aureus and Streptococcus pyogenes, are becoming increasingly antibiotic-resistant. Despite the urgency, only a few new antibiotics have been approved to address these infections. Although cannabinoids have been noted for their antibacterial properties, a comprehensive review of their effects on these bacteria has been lacking. Objective: This systematic review examines the antibacterial activity of cannabinoids against S. aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains, and S. pyogenes. Methods: Databases, including CINAHL, Cochrane, Medline, Scopus, Web of Science, and LILACS, were searched. Of 3510 records, 24 studies met the inclusion criteria, reporting on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of cannabinoids. Results: Cannabidiol (CBD) emerged as the most effective cannabinoid, with MICs ranging from 0.65 to 32 mg/L against S. aureus, 0.5 to 4 mg/L for MRSA, and 1 to 2 mg/L for VRSA. Other cannabinoids, such as cannabichromene, cannabigerol (CBG), and delta-9-tetrahydrocannabinol (Δ9-THC), also exhibited significant antistaphylococcal activity. CBD, CBG, and Δ9-THC also showed efficacy against S. pyogenes, with MICs between 0.6 and 50 mg/L. Synergistic effects were observed when CBD and essential oils from Cannabis sativa when combined with other antibacterial agents. Conclusion: Cannabinoids’ antibacterial potency is closely linked to their structure–activity relationships, with features like the monoterpene region, aromatic alkyl side chain, and aromatic carboxylic groups enhancing efficacy, particularly in CBD and its cyclic forms. These results highlight the potential of cannabinoids in developing therapies for resistant strains, though further research is needed to confirm their clinical effectiveness. Full article
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