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New Insights in Bioactive Compounds as Antibiofilm Agents

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 4051

Special Issue Editors


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Guest Editor
Department of Medical, Oral, and Biotechnological Sciences, G. d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm formation mechanisms; role of biofilm formation in the pathogenesis of cystic fibrosis lung infections; drug repurposing to identify new molecules with antibacterial activity; antibiofilm strategies
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Medical, Oral and Biotechnological Sciences, Center for Advanced Studies and Technology (CAST), Gabriele d’Annunzio University of Chieti-Pescara, 66100 Chieti, Italy
Interests: biofilm formation; cystic fibrosis; lung infections; probiotics; antibiotic resistance; antimicrobial compounds; Pseudomonas aeruginosa; Stenotrophomonas maltophilia; bacterial pathogenesis; microbial cooperation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Most human chronic infectious diseases are caused by microorganisms growing as biofilms, 3D self-organized communities adhered to abiotic and biotic surfaces inherently resistant to antibiotics, disinfectants, and immune system effectors. Novel strategies to control biofilm-associated infections are, therefore, needed. Natural products offer a vast array of chemical structures with various biological properties. For these reasons, they have been recently exploited in the search for potential biofilm inhibitors. Within this framework, this Special Issue aims to collect high-quality contributions focused on the impact of bioactive compounds isolated from several natural sources—such as plants, lichens, algae, microorganisms, animals, and humans—on all aspects of biofilm research. We hope to add needed knowledge for the development of bioactive compounds as novel drugs to combat bacterial biofilms and as antibiotic adjuvants to restore the therapeutic efficacy of current antibiotics.

Dr. Giovanni Di Bonaventura
Dr. Arianna Pompilio
Guest Editors

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Keywords

  • bioactive natural compounds
  • microbial biofilms
  • biofilm-associated infections

Published Papers (3 papers)

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Research

0 pages, 14539 KiB  
Article
Inhibition of Biofilm Formation in Cutibacterium acnes, Staphylococcus aureus, and Candida albicans by the Phytopigment Shikonin
by Yong-Guy Kim, Jin-Hyung Lee, Sanghun Kim, Sunyoung Park, Yu-Jeong Kim, Choong-Min Ryu, Hwi Won Seo and Jintae Lee
Int. J. Mol. Sci. 2024, 25(4), 2426; https://doi.org/10.3390/ijms25042426 - 19 Feb 2024
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Abstract
Skin microbiota, such as acne-related Cutibacterium acnes, Staphylococcus aureus, and fungal Candida albicans, can form polymicrobial biofilms with greater antimicrobial tolerance to traditional antimicrobial agents and host immune systems. In this study, the phytopigment shikonin was investigated against single-species and [...] Read more.
Skin microbiota, such as acne-related Cutibacterium acnes, Staphylococcus aureus, and fungal Candida albicans, can form polymicrobial biofilms with greater antimicrobial tolerance to traditional antimicrobial agents and host immune systems. In this study, the phytopigment shikonin was investigated against single-species and multispecies biofilms under aerobic and anaerobic conditions. Minimum inhibitory concentrations of shikonin were 10 µg/mL against C. acnes, S. aureus, and C. albicans, and at 1–5 µg/mL, shikonin efficiently inhibited single biofilm formation and multispecies biofilm development by these three microbes. Shikonin increased porphyrin production in C. acnes, inhibited cell aggregation and hyphal formation by C. albicans, decreased lipase production, and increased hydrophilicity in S. aureus. In addition, shikonin at 5 or 10 µg/mL repressed the transcription of various biofilm-related genes and virulence-related genes in C. acnes and downregulated the gene expression levels of the quorum-sensing agrA and RNAIII, α-hemolysin hla, and nuclease nuc1 in S. aureus, supporting biofilm inhibition. In addition, shikonin prevented multispecies biofilm development on porcine skin, and the antimicrobial efficacy of shikonin was recapitulated in a mouse infection model, in which it promoted skin regeneration. The study shows that shikonin inhibits multispecies biofilm development by acne-related skin microbes and might be useful for controlling bacterial infections. Full article
(This article belongs to the Special Issue New Insights in Bioactive Compounds as Antibiofilm Agents)
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12 pages, 2216 KiB  
Article
Antimicrobial and Cytotoxic Activities of Water-Soluble Isoxazole-Linked 1,3,4-Oxadiazole with Delocalized Charge: In Vitro and In Vivo Results
by Bartłomiej Dudek, Urszula Bąchor, Ewa Drozd-Szczygieł, Malwina Brożyna, Piotr Dąbrowski, Adam Junka and Marcin Mączyński
Int. J. Mol. Sci. 2023, 24(22), 16033; https://doi.org/10.3390/ijms242216033 - 7 Nov 2023
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Abstract
The distinct structure of cationic organic compounds plays a pivotal role in enhancing their water solubility, which in turn influences their bioavailability. A representative of these compounds, which contains a delocalized charge, is 5-amino-2-(5-amino-3-methyl-1,2-oxazol-4-yl)-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-ylium bromide (ED). The high-water solubility of ED obviates the [...] Read more.
The distinct structure of cationic organic compounds plays a pivotal role in enhancing their water solubility, which in turn influences their bioavailability. A representative of these compounds, which contains a delocalized charge, is 5-amino-2-(5-amino-3-methyl-1,2-oxazol-4-yl)-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-ylium bromide (ED). The high-water solubility of ED obviates the need for potentially harmful solvents during in vitro testing. The antibacterial and antifungal activities of the ED compound were assessed in vitro using the microtiter plate method and a biocellulose-based biofilm model. Additionally, its cytotoxic effects on wound bed fibroblasts and keratinocytes were examined. The antistaphylococcal activity of ED was also evaluated using an in vivo larvae model of Galleria mellonella. Results indicated that ED was more effective against Gram-positive bacteria than Gram-negative ones, exhibiting bactericidal properties. Furthermore, ED demonstrated greater efficacy against biofilms formed by Gram-positive bacteria. At bactericidal concentrations, ED was non-cytotoxic to fibroblasts and keratinocytes. In in vivo tests, ED was non-toxic to the larvae. When co-injected with a high load of S. aureus, it reduced the average larval mortality by approximately 40%. These findings suggest that ED holds promise for further evaluation as a potential treatment for biofilm-based wound infections, especially those caused by Gram-positive pathogens like S. aureus. Full article
(This article belongs to the Special Issue New Insights in Bioactive Compounds as Antibiofilm Agents)
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23 pages, 9091 KiB  
Article
Bromotyrosine-Derived Metabolites from a Marine Sponge Inhibit Pseudomonas aeruginosa Biofilms
by Tam M. T. Tran, Russell S. Addison, Rohan A. Davis and Bernd H. A. Rehm
Int. J. Mol. Sci. 2023, 24(12), 10204; https://doi.org/10.3390/ijms241210204 - 16 Jun 2023
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Abstract
Pseudomonas aeruginosa forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the [...] Read more.
Pseudomonas aeruginosa forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A–C and their combinations with clinically used antibiotics. Wild-type P. aeruginosa strain and its isogenic exopolysaccharide-deficient mutants were employed to determine the interference of the compounds with biofilm matrix components. We identified that ianthelliformisamines A and B worked synergistically with ciprofloxacin to kill planktonic and biofilm cells. Ianthelliformisamines A and B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin to 1/3 and 1/4 MICs, respectively. In contrast, ianthelliformisamine C (MIC = 53.1 µg/mL) alone exhibited bactericidal effects dose-dependently on both free-living and biofilm populations of wild-type PAO1, PAO1ΔpslA (Psl deficient), PDO300 (alginate overproducing and mimicking clinical isolates), and PDO300Δalg8 (alginate deficient). Interestingly, the biofilm of the clinically relevant mucoid variant PDO300 was more susceptible to ianthelliformisamine C than strains with impaired polysaccharide synthesis. Ianthelliformisamines exhibited low cytotoxicity towards HEK293 cells in the resazurin viability assay. Mechanism of action studies showed that ianthelliformisamine C inhibited the efflux pump of P. aeruginosa. Metabolic stability analyses indicated that ianthelliformisamine C is stable and ianthelliformisamines A and B are rapidly degraded. Overall, these findings suggest that the ianthelliformisamine chemotype could be a promising candidate for the treatment of P. aeruginosa biofilms. Full article
(This article belongs to the Special Issue New Insights in Bioactive Compounds as Antibiofilm Agents)
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