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Antibiofilm and Antivirulence Activities of Natural Compounds
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Antibiofilm and Antivirulence Activities of Natural Compounds

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

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 28938

Special Issue Editor

Prof. Dr. Jintae Lee

E-Mail Website
Guest Editor
School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
Interests: antibiotic resistance; biofilm; bionanotechnology; quorum sensing; S. aureus; C. albicans

Special Issue Information

Dear Colleagues,

Due to the high incidence of multidrug-resistant bacteria, traditional antibiotics and biocide treatments are often unsatisfactory. Antivirulence strategies aim to reduce pathogenesis and its consequences without affecting bacterial growth in order to reduce the chance of the emergence of drug resistance. Antivirulence approaches include the inhibition of bacterial adhesion, biofilm formation, quorum sensing, and toxin production. In particular, bacterial biofilms are metabolically less active and grow more slowly compared to free-floating counterparts, which facilitates the acquisition of antibiotic resistance. The aim of this Special Issue is to present a collection of manuscripts that explore newly discovered antibiofilm agents as well as antivirulence agents from diverse natural resources.

Potential topics may include but are not limited to:

  • Identification and molecular study of antibiofilm compounds from phytochemicals, microbial metabolites, and other natural sources;
  • Identification and molecular study of antivirulence compounds targeting bacterial virulence factors such as adhesins, quorum sensing, toxins, and immune evasive responses from natural resources;
  • Molecular approaches against bacterial drug resistance and persisters.

As Guest Editor for this Special Issue, I would like all researchers to submit their findings related to antibiofilm and antivirulence agents with molecular study for action of modes for the upcoming Special Issue on “Antibiofilm and Antivirulence Activities of Natural Compounds” in the International Journal of Molecular Sciences.

Prof. Dr. Jintae Lee
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • antibiofilm
  • antivirulence
  • adhesins
  • bacterial drug resistance
  • natural compounds
  • persister
  • quorum sensing
  • toxins

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Published Papers (7 papers)

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Research

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18 pages, 7339 KiB  
Article
The Antimicrobial Activity of Curcumin and Xanthohumol on Bacterial Biofilms Developed over Dental Implant Surfaces
by Andrea Alonso-Español, Enrique Bravo, Honorato Ribeiro-Vidal, Leire Virto, David Herrera, Bettina Alonso and Mariano Sanz
Int. J. Mol. Sci. 2023, 24(3), 2335; https://doi.org/10.3390/ijms24032335 - 25 Jan 2023
Cited by 13 | Viewed by 3301
Abstract
In search for natural products with antimicrobial properties for use in the prevention and treatment of peri-implantitis, the purpose of this investigation was to evaluate the antimicrobial activity of curcumin and xanthohumol, using an in vitro multi-species dynamic biofilm model including Streptococcus oralis, [...] Read more.
In search for natural products with antimicrobial properties for use in the prevention and treatment of peri-implantitis, the purpose of this investigation was to evaluate the antimicrobial activity of curcumin and xanthohumol, using an in vitro multi-species dynamic biofilm model including Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. The antimicrobial activities of curcumin (5 mM) and xanthohumol (100 μM) extracts, and the respective controls, were evaluated with 72-h biofilms formed over dental implants by their submersion for 60 seconds. The evaluation was assessed by quantitative polymerase chain reaction (qPCR), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). For the data analysis, comparisons were tested applying ANOVA tests with post-hoc Bonferroni corrections to evaluate the antimicrobial activity of both extracts. With qPCR, statistically significant reductions in bacterial counts were observed for curcumin and xanthohumol, when compared to the negative control. The results with CLSM and SEM were consistent with those reported with qPCR. It was concluded that both curcumin and xanthohumol have demonstrated antimicrobial activity against the six bacterial species included in the dynamic in vitro biofilm model used. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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12 pages, 8049 KiB  
Article
Hydroquinones Inhibit Biofilm Formation and Virulence Factor Production in Staphylococcus aureus
by Sanghun Kim, Jin-Hyung Lee, Yong-Guy Kim, Yulong Tan and Jintae Lee
Int. J. Mol. Sci. 2022, 23(18), 10683; https://doi.org/10.3390/ijms231810683 - 14 Sep 2022
Cited by 6 | Viewed by 1894
Abstract
Staphylococcus aureus is one of the major pathogens responsible for antimicrobial resistance-associated death. S. aureus can secrete various exotoxins, and staphylococcal biofilms play critical roles in antibiotic tolerance and the persistence of chronic infections. Here, we investigated the inhibitory effects of 18 hydroquinones [...] Read more.
Staphylococcus aureus is one of the major pathogens responsible for antimicrobial resistance-associated death. S. aureus can secrete various exotoxins, and staphylococcal biofilms play critical roles in antibiotic tolerance and the persistence of chronic infections. Here, we investigated the inhibitory effects of 18 hydroquinones on biofilm formation and virulence factor production by S. aureus. It was found that 2,5-bis(1,1,3,3-tetramethylbutyl) hydroquinone (TBHQ) at 1 µg/mL efficiently inhibits biofilm formation by two methicillin-sensitive and two methicillin-resistant S. aureus strains with MICs of 5 µg/mL, whereas the backbone compound hydroquinone did not (MIC > 400 µg/mL). In addition, 2,3-dimethylhydroquinone and tert-butylhydroquinone at 50 µg/mL also exhibited antibiofilm activity. TBHQ at 1 µg/mL significantly decreased the hemolytic effect and lipase production by S. aureus, and at 5–50 µg/mL was non-toxic to the nematode Caenorhabditis elegans and did not adversely affect Brassica rapa seed germination or growth. Transcriptional analyses showed that TBHQ suppressed the expression of RNAIII (effector of quorum sensing). These results suggest that hydroquinones, particularly TBHQ, are potentially useful for inhibiting S. aureus biofilm formation and virulence. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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21 pages, 5512 KiB  
Article
The Xanthophyll Carotenoid Lutein Reduces the Invasive Potential of Pseudomonas aeruginosa and Increases Its Susceptibility to Tobramycin
by Christian Emmanuel Mahavy, Adeline Mol, Blandine Andrianarisoa, Pierre Duez, Mondher El Jaziri, Marie Baucher and Tsiry Rasamiravaka
Int. J. Mol. Sci. 2022, 23(13), 7199; https://doi.org/10.3390/ijms23137199 - 28 Jun 2022
Cited by 6 | Viewed by 1876
Abstract
Recently, the xanthophyll carotenoid lutein has been qualified as a potential quorum sensing (QS) and biofilm inhibitor against Pseudomonas aeruginosa. To address the potential of this xanthophyll compound as a relevant antivirulence agent, we investigated in depth its impact on the invasion capabilities [...] Read more.
Recently, the xanthophyll carotenoid lutein has been qualified as a potential quorum sensing (QS) and biofilm inhibitor against Pseudomonas aeruginosa. To address the potential of this xanthophyll compound as a relevant antivirulence agent, we investigated in depth its impact on the invasion capabilities and aggressiveness of P. aeruginosa PAO1, which rely on the bacterial ability to build and maintain protective barriers, use different types of motilities and release myriad virulence factors, leading to host cell and tissue damages. Our data, obtained on the PAO1 strain, indicate that all-trans lutein (Lut; 22 µM) disrupts biofilm formation and disorganizes established biofilm structure without affecting bacterial viability, while improving the bactericidal activity of tobramycin against biofilm-encapsulated PAO1 cells. Furthermore, this xanthophyll affects PAO1 twitching and swarming motilities while reducing the production of the extracellular virulence factors pyocyanin, elastase and rhamnolipids as well as the expression of the QS-regulated lasB and rhlA genes without inhibiting the QS-independent aceA gene. Interestingly, the expression of the QS regulators rhlR/I and lasR/I is significantly reduced as well as that of the global virulence factor regulator vfr, which is suggested to be a major target of Lut. Finally, an oxidative metabolite of Lut, 3′-dehydrolutein, induces a similar inhibition phenotype. Taken together, lutein-type compounds represent potential agents to control the invasive ability and antibiotic resistance of P. aeruginosa. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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14 pages, 7587 KiB  
Article
Collagen Peptide in a Combinatorial Treatment with Lactobacillus rhamnosus Inhibits the Cariogenic Properties of Streptococcus mutans: An In Vitro Study
by Hee-Young Jung, Jian-Na Cai, Sung Chul Yoo, Seon-Hwa Kim, Jae-Gyu Jeon and Dongyeop Kim
Int. J. Mol. Sci. 2022, 23(3), 1860; https://doi.org/10.3390/ijms23031860 - 7 Feb 2022
Cited by 6 | Viewed by 2985
Abstract
Dental caries is caused by the formation of cariogenic biofilm, leading to localized areas of enamel demineralization. Streptococcus mutans, a cariogenic pathogen, has long been considered as a microbial etiology of dental caries. We hypothesized that an antagonistic approach using a prebiotic [...] Read more.
Dental caries is caused by the formation of cariogenic biofilm, leading to localized areas of enamel demineralization. Streptococcus mutans, a cariogenic pathogen, has long been considered as a microbial etiology of dental caries. We hypothesized that an antagonistic approach using a prebiotic collagen peptide in combination with probiotic Lactobacillus rhamnosus would modulate the virulence of this cariogenic biofilm. In vitro S. mutans biofilms were formed on saliva-coated hydroxyapatite discs, and the inhibitory effect of a combination of L. rhamnosus and collagen peptide on S. mutans biofilms were evaluated using microbiological, biochemical, confocal imaging, and transcriptomic analyses. The combination of L. rhamnosus with collagen peptide altered acid production by S. mutans, significantly increasing culture pH at an early stage of biofilm formation. Moreover, the 3D architecture of the S. mutans biofilm was greatly compromised when it was in the presence of L. rhamnosus with collagen peptide, resulting in a significant reduction in exopolysaccharide with unstructured and mixed bacterial organization. The presence of L. rhamnosus with collagen peptide modulated the virulence potential of S. mutans via down-regulation of eno, ldh, and atpD corresponding to acid production and proton transportation, whereas aguD associated with alkali production was up-regulated. Gly-Pro-Hyp, a common tripeptide unit of collagen, consistently modulated the cariogenic potential of S. mutans by inhibiting acid production, similar to the bioactivity of a collagen peptide. It also enhanced the relative abundance of commensal streptococci (S. oralis) in a mixed-species biofilm by inhibiting S. mutans colonization and dome-like microcolony formation. This work demonstrates that food-derived synbiotics may offer a useful means of disrupting cariogenic communities and maintaining microbial homeostasis. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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20 pages, 6711 KiB  
Article
Pyranoanthocyanins Interfering with the Quorum Sensing of Pseudomonas aeruginosa and Staphylococcus aureus
by Patrícia Coelho, Joana Oliveira, Iva Fernandes, Paula Araújo, Ana Rita Pereira, Paula Gameiro and Lucinda J. Bessa
Int. J. Mol. Sci. 2021, 22(16), 8559; https://doi.org/10.3390/ijms22168559 - 9 Aug 2021
Cited by 19 | Viewed by 3402
Abstract
Bacterial quorum sensing (QS) is a cell-cell communication system that regulates several bacterial mechanisms, including the production of virulence factors and biofilm formation. Thus, targeting microbial QS is seen as a plausible alternative strategy to antibiotics, with potentiality to combat multidrug-resistant pathogens. Many [...] Read more.
Bacterial quorum sensing (QS) is a cell-cell communication system that regulates several bacterial mechanisms, including the production of virulence factors and biofilm formation. Thus, targeting microbial QS is seen as a plausible alternative strategy to antibiotics, with potentiality to combat multidrug-resistant pathogens. Many phytochemicals with QS interference activity are currently being explored. Herein, an extract and a compound of bioinspired origin were tested for their ability to inhibit biofilm formation and interfere with the expression of QS-related genes in Pseudomonas aeruginosa and Staphylococcus aureus. The extract, a carboxypyranoanthocyanins red wine extract (carboxypyrano-ant extract), and the pure compound, carboxypyranocyanidin-3-O-glucoside (carboxypyCy-3-glc), did not cause a visible effect on the biofilm formation of the P. aeruginosa biofilms; however, both significantly affected the formation of biofilms by the S. aureus strains, as attested by the crystal violet assay and fluorescence microscopy. Both the extract and the pure compound significantly interfered with the expression of several QS-related genes in the P. aeruginosa and S. aureus biofilms, as per reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results. Indeed, it was possible to conclude that these molecules interfere with QS at distinct stages and in a strain-specific manner. An extract with anti-QS properties could be advantageous because it is easily obtained and could have broad, antimicrobial therapeutic applications if included in topical formulations. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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Review

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18 pages, 1865 KiB  
Review
Bacterial Cellulose: Production, Characterization, and Application as Antimicrobial Agent
by Dibyajit Lahiri, Moupriya Nag, Bandita Dutta, Ankita Dey, Tanmay Sarkar, Siddhartha Pati, Hisham Atan Edinur, Zulhisyam Abdul Kari, Noor Haslina Mohd Noor and Rina Rani Ray
Int. J. Mol. Sci. 2021, 22(23), 12984; https://doi.org/10.3390/ijms222312984 - 30 Nov 2021
Cited by 115 | Viewed by 9571
Abstract
Bacterial cellulose (BC) is recognized as a multifaceted, versatile biomaterial with abundant applications. Groups of microorganisms such as bacteria are accountable for BC synthesis through static or agitated fermentation processes in the presence of competent media. In comparison to static cultivation, agitated cultivation [...] Read more.
Bacterial cellulose (BC) is recognized as a multifaceted, versatile biomaterial with abundant applications. Groups of microorganisms such as bacteria are accountable for BC synthesis through static or agitated fermentation processes in the presence of competent media. In comparison to static cultivation, agitated cultivation provides the maximum yield of the BC. A pure cellulose BC can positively interact with hydrophilic or hydrophobic biopolymers while being used in the biomedical domain. From the last two decades, the reinforcement of biopolymer-based biocomposites and its applicability with BC have increased in the research field. The harmony of hydrophobic biopolymers can be reduced due to the high moisture content of BC in comparison to hydrophilic biopolymers. Mechanical properties are the important parameters not only in producing green composite but also in dealing with tissue engineering, medical implants, and biofilm. The wide requisition of BC in medical as well as industrial fields has warranted the scaling up of the production of BC with added economy. This review provides a detailed overview of the production and properties of BC and several parameters affecting the production of BC and its biocomposites, elucidating their antimicrobial and antibiofilm efficacy with an insight to highlight their therapeutic potential. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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17 pages, 952 KiB  
Review
Campylobacter Biofilms: Potential of Natural Compounds to Disrupt Campylobacter jejuni Transmission
by Bassam A. Elgamoudi and Victoria Korolik
Int. J. Mol. Sci. 2021, 22(22), 12159; https://doi.org/10.3390/ijms222212159 - 10 Nov 2021
Cited by 24 | Viewed by 4418
Abstract
Microbial biofilms occur naturally in many environmental niches and can be a significant reservoir of infectious microbes in zoonotically transmitted diseases such as that caused by Campylobacter jejuni, the leading cause of acute human bacterial gastroenteritis world-wide. The greatest challenge in reducing [...] Read more.
Microbial biofilms occur naturally in many environmental niches and can be a significant reservoir of infectious microbes in zoonotically transmitted diseases such as that caused by Campylobacter jejuni, the leading cause of acute human bacterial gastroenteritis world-wide. The greatest challenge in reducing the disease caused by this organism is reducing transmission of C. jejuni to humans from poultry via the food chain. Biofilms enhance the stress tolerance and antimicrobial resistance of the microorganisms they harbor and are considered to play a crucial role for Campylobacter spp. survival and transmission to humans. Unconventional approaches to control biofilms and to improve the efficacy of currently used antibiotics are urgently needed. This review summarizes the use plant- and microorganism-derived antimicrobial and antibiofilm compounds such as essential oils, antimicrobial peptides (AMPs), polyphenolic extracts, algae extracts, probiotic-derived factors, d-amino acids (DAs) and glycolipid biosurfactants with potential to control biofilms formed by Campylobacter, and the suggested mechanisms of their action. Further investigation and use of such natural compounds could improve preventative and remedial strategies aimed to limit the transmission of campylobacters and other human pathogens via the food chain. Full article
(This article belongs to the Special Issue Antibiofilm and Antivirulence Activities of Natural Compounds)
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