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Oral Pathogens and Their Antibiotics from Marine Organisms: A Systematic Review of New Drugs for Novel Drug Targets
J Dent Hyg Sci 2024;24:84-96
Published online June 30, 2024;
© 2024 Korean Society of Dental Hygiene Science.

Sehyeok Im1 ,2, Jun Hyuck Lee1 ,2,†, and Youn-Soo Shim3,†

1Division of Life Sciences, Korea Polar Research Institute, Incheon 21990, 2Department of Polar Sciences, University of Science and Technology, Incheon 21990, 3Department of Dental Hygiene, Sunmoon University, Asan 31460, Korea
Correspondence to: Youn-Soo Shim,
Department of Dental Hygiene, Sunmoon University, 70 Sunmoon-ro, 221 beon-gil, Asan 31460, Korea
Tel: +82-41-530-2740, Fax: +82-41-530-2726, E-mail:
Jun Hyuck Lee,
Division of Life Sciences, Korea Polar Research Institute, 26 Songdomirae-ro, Incheon 21990, Korea
Tel: +82-32-760-5555, Fax: +82-32-760-5509, E-mail:
Received May 1, 2024; Revised May 30, 2024; Accepted June 5, 2024.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Recent studies have elucidated the quorum-sensing mechanisms, biofilm formation, inter-pathogen interactions, and genes related to oral pathogens. This review aims to explore the recent expansion of drug targets against oral pathogens and summarize the current research on novel antibiotic substances derived from marine organisms that target oral pathogens.
Methods: A comprehensive literature review summarized the novel mechanisms pertaining to quorum-sensing signal transmission systems, biofilm formation, and metabolite exchange in oral pathogens. The amino acid sequences of the 16 proteins identified as potential drug targets were systematically classified and compared across various oral microorganisms.
Results: Through a literature review, we identified nine studies researching quorum sensing signaling inhibitors targeting oral pathogens. A comparison of the amino acid sequences of 16 potential drug targets in oral microorganisms revealed significant differences between oral pathogens and beneficial oral symbiotic microorganisms. These findings imply that it is possible to design drugs that can bind more selectively to oral pathogens.
Conclusion: By summarizing the results of recent research on the signaling mechanisms that cause pathogenicity, new drug targets against oral pathogens were proposed. Additionally, the current status of developing new antibiotics for oral pathogens using recently developed quorum sensing inhibitors and natural products derived from marine organisms was introduced. Consequently, marine natural products can be used to develop drugs targeting new proteins in oral pathogens.
Keywords : Antibiotics, Biofilms, Marine organisms, Oral pathogen, Quorum sensing


The human oral cavity contains a complex community of microorganisms (including oral pathogens) that exert a substantial influence on dental and systemic health. Various microbial niches appear in the tissues of the human oral cavity owing to factors such as nutritional content, pH, oxygen concentration, and metabolic properties of the microbial ecosystem1-3). Biofilm formation in the oral environment is a critical mechanism for these oral pathogens. While biofilms naturally occur in healthy teeth, the accumulation of successive dental biofilms can play a critical role in the development of diseases, such as dental caries, gingivitis, and periodontitis4,5). Furthermore, bacteria from dental biofilms may cause systemic diseases such as endocarditis, diabetes mellitus, atherosclerosis, rheumatoid arthritis, and orodigestive cancer through bacteremia or indirect manners6-10). Research on oral pathogens is important to understand their roles in various systemic diseases and conditions. Poor oral hygiene and periodontal health can affect systemic health and vice versa11). Understanding the relationship between oral pathogens and systemic diseases can improve diagnosis, prevention, and treatment strategies. Therefore, research on oral pathogens is crucial to improve overall oral and systemic health outcomes.

Oral biofilms are formed in several stages and involve various bacteria. Saccharolytic bacteria, such as Streptococcus, Lactobacillus, and Actinomyces species, are prominent in the formation of dental caries by creating acids that erode tooth enamel1,12). Various organisms living in the oral cavity, including these species, are known oral pathogens. Proteolytic bacteria such as Prevotella and Porphyromonas species break down proteins into amino acids and further degrade these amino acids, generating short-chain fatty acids, ammonia, sulfur compounds, and indole/skatole, which serve as virulent factors contributing to periodontitis and oral malodor13,14). Porphyromonas gingivalis is a common cause of chronic periodontitis and an indicator of disease progression15,16). It affects the proliferation of oral tumor cells and modifies epidermal growth factor receptor signaling, which is relevant to the development of oral tumors and colorectal cancer. They play key roles in the formation of multispecies dental biofilms17). Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae are the main cause of infections, ranging from pneumonia to bloodstream infections, and their presence in the oral cavity can lead to systemic and opportunistic infections (Fig. 1)18).

Fig. 1. Stages of oral biofilm formation and dispersion. Several oral pathogens use quorum-sensing signaling to form biofilms. Additionally, direct interactions with other pathogens or signaling using secondary metabolites occur. Biofilm dispersion can be largely divided into active dispersion by signals of the microorganism itself and passive dispersion by external physical stimulation. EPS: extracellular polymeric substances.

Additionally, other species and types of oral pathogens live in the human oral cavity. For example, Candida albicans is a fungus that contributes to oral infections, particularly in immunocompromised individuals19,20). Aggregatibacter actinomycetemcomitans, Filifactor alocis, Staphylococcus aureus, Aspergillus fumigatus, Mucor, Cryptococcus, Corynebacterium, Haemophilus influenzae, Haemophilus parainfluenzae, and Neisseria species are well-known oral pathogens21-24).

These bacteria rapidly colonize various surfaces within the oral tissue despite the turbulent environment within the human oral cavity. Colonization begins within several minutes and extensive microbial deposition occurs within a few hours. Biofilm development in the oral cavity can be divided into adhesion/coaggregation, microbial interactions, and extracellular matrix formation stages25,26). Streptococci participated in all stages, and a wide variety of bacteria participated in each stage (Table 1). Oral streptococci express numerous adhesins on their cell surface. Adhesins are key elements that allow streptococci to anchor to human tissues and other bacterial cells27). Oral streptococci, including commensal, cariogenic, and extraoral streptococci, express a family of proteins called antigens I/II (AgI/II). AgI/II allows streptococci to attach to enamel surfaces and aggregate with other bacteria by binding to the salivary agglutinin glycoprotein gp34028,29).

Representative Examples of Participating Bacteria throughout the Oral Biofilm Formation Stages

Adhesion/coaggregation Interaction Matrix production

Pathogen Description Pathogen Description Pathogen Description
Streptococci AgI/II proteins result in aggregation Early colonizing streptococci Produce acids from sugars Streptococcus mutans Produce insoluble glucans, an important component of biofilm matrix
Porphyromonas gingivalis Bindto pre-existing Streptococcus gordonii biofilm Aggregatibacter actinomycetemcomitans Utilize lactate produced by streptococci Enterococcus faecalis Forma structural biofilm scaffold with proteins and extracellular DNA
Fusobacterium nucleatum Coaggregate with almost all other oral bacteria Veillonella sp. Participate in numerous mutualistic interactions Neisseria meningitides


This review introduces the recent studies on the various pathogenic mechanisms of oral pathogens. Specifically, we describe the direct interactions between pathogens, quorum sensing signaling, and metabolite exchange that occur during biofilm formation by oral pathogens. We also summarized the virulence factors involved in biofilm formation by oral pathogens. These newly identified mechanisms of pathogenic virulence factors may provide new drug targets for the development of novel antibiotics against oral pathogens. Furthermore, we suggested methods for selective drug development against specific oral pathogens through a sequence comparison of drug target proteins that have not been previously introduced. Additionally, we present the possibility of discovering new antibacterial substances in marine organisms based on recent successful findings.

Materials and Methods

1.Literature and protein sequence database search

A literature search was performed using PubMed ( and Google Scholar ( databases. The Basic Local Alignment Search Tool (BLAST) was used to identify homologous protein sequences in other species.

2.Protein sequence identity and similarity calculation

Sixteen well-known drug target proteins for general pathogens were selected through a literature review using PubMed and Google Scholar. The sequences of these 16 proteins from the pathogen P. gingivalis were retrieved from the UniProt Knowledge Base (UniProtKB) protein sequence database. Using the 16 protein sequences from P. gingivalis as queries, homologous proteins from other oral microorganisms were searched in the UniProtKB protein sequence database. The search results were compiled by one researcher and subsequently reviewed by two authors who were not involved in the initial search process. Protein sequence alignments and analyses were performed using the web-based multiple alignment program ClustalW (

Results and Discussion

1.The demand to develop new antibiotics

Antibiotics prescribed for oral health are commonly used in dentistry for periodontal infections, non-periodontal infections, localized infections, focal infections, and as preventive measures during dental procedures. Antibiotic treatment involves direct application at the site of infection or systemic administration via ingestion. It is crucial to choose an appropriate approach by targeting antibiotic therapy specifically for oral pathogens, while preserving beneficial oral commensal bacteria, thereby inhibiting the growth of oral pathogens30,31).

Overuse and misuse of antibiotics in odontogenic infections can promote the colonization of resistant bacteria, and antibiotic-resistant gene-containing plasmids can spread across a broad niche of bacteria through transmission30,31). The emergence of multidrug-resistant oral pathogens that render conventional treatments ineffective has become a critical global health concern since conventional treatments become ineffective32). The development of novel antimicrobial agents is crucial owing to the increasing threat of multidrug-resistant oral pathogens and limited options for therapy33,34). Therefore, it is important to identify valuable sources of antibiotics in natural ecosystems35-37).

2.Interpreting recent studies

Marine organisms are rich sources of antibiotics. Marine sponges, such as those from the phylum Porifera, produce bioactive compounds that can be used to improve human health38). Natural compounds derived from marine microorganisms (including bacteria, fungi, actinomycetes, and cyanobacteria) exhibit promising antimicrobial properties and can act against various antibiotic-resistant pathogenic strains. Antibiotics produced by bacteria living in marine environments have also been studied; diverse metabolites have been isolated and their chemical structures elucidated39). Actinomycetes (specifically, marine actinomycetes) have been identified as potential producers of novel antibiotics, with strains such as Streptomyces sampsonii, Streptomyces halstedii, and Nocardiopsis alba showing significant antibiotic activity against various pathogens40,41). Additionally, marine-derived natural products have been explored for their anti-biofilm activity, and 129 marine-derived natural products and their synthetic analogs have been reviewed for their effectiveness in combating biofilm formation (Table 2)42).

Antimicrobial Substances against Oral Pathogens Derived from Marine Organisms

Natural compound Source Description Reference
Fucoidan Fucus vesiculosus, Cladosiphon okamuranus, Laminaria japonica, and many other brown macroalgal species ∙Long chain sulfated and fucose-rich polysaccharide. 43∼46
∙Broad pharmacological effects include antibacterial, antiviral, and anti-inflammatory effects.
∙Antimicrobial activity against Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis.
Halistanol sulfate Halichondria moori from marine sponge ∙Inhibition of biofilm formation and reduction of biofilm-associated gene expression in S. mutans and Streptococcus sanguinis. 47, 48
Mayamycin Streptomyces sp. HB202 bacteria isolated from marine sponge ∙Inhibitory effect against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. 49
Salinisporamycin Salinispora sp. marine bacteria from bottom sediments ∙Inhibition of adenocarcinoma cell growth. 50
∙Antimicrobial activity against S. aureus and C. albicans.
Fridamycin A/D Streptomyces marine bacteria from bottom sediments ∙Antibacterial activity against multidrug-resistant S. aureus. 51
Callinectin Callinectes sapidus from blue crab ∙Antibacterial activity against Gram-negative bacteria. 53
Coumarin Diverse group of algae, marine fungi,and ascidians ∙Inhibition of biofilm formation of P. gingivalis through reducing AI-2 activity. 54, 55

Biologically active compounds have been identified in several brown algae species. Fucoidan is a long chain, sulfated, fucose-rich polysaccharide found in the cell walls of brown macroalgal species, including Fucus vesiculosus, Cladosiphon okamuranus, Laminaria japonica, and Undaria pinnatifida43). It is widely studied owing to its diverse pharmacological effects (including antitumor effects) that promote the apoptosis of cancer cells44-46), as well as its antiviral, anti-inflammatory, anti-allergic, and hypotensive effects44).

Microbial symbionts in marine sponges and corals produce bioactive compounds with antimicrobial properties. Halistanol sulfate, discovered in the sponge Halichondria moori, exhibits antibacterial activity against Streptococcus mutans, which is the main etiological agent of human dental caries47,48). Halistanol sulfate A exhibited the strongest antibacterial effect against S. mutans, inhibits biofilm formation in planktonic cells, and reduces the expression of biofilm-related genes (gtfB, gtfC, and gbpB)47,48). Halistanol sulfate A also inhibits Streptococcus sanguinis at higher concentrations47). Mayamycin is an aromatic polyketide identified in a symbiotic Streptomyces sp. strain isolated from the marine sponge Halichondria panicea. It has shown significant pharmacological activities, including cytotoxicity against human cancer cell lines and antimicrobial activity against various bacteria such as P. aeruginosa and methicillin-resistant S. aureus49). Marine sediment bacteria produce diverse compounds with potential antibiotic properties. For example, salinisporamycin, a rifamycin antibiotic isolated from the marine actinomycete Salinispora arenicola, inhibits the growth of human lung adenocarcinoma cells and exhibits antimicrobial activity against P. aeruginosa and C. albicans50). Similarly, Fridamycin A and Fridamycin D, identified in a Streptomyces sp. strain from the marine sediment of the Philippine archipelago, exhibit antibacterial activity against multidrug-resistant S. aureus51). Additionally, a Pseudomonas sp. associated with the soft coral Sinularia polydactyla shows antibacterial activity against Streptococcus equi subspecies, although the specific antibacterial substance remains unidentified52).

Potential antibiotic candidates are found not only in bacteria but also in various marine organisms. For example, blue crabs (Callinectes sapidus) synthesize the antimicrobial peptide called callinectin in their hemolymph, which is effective against gram-negative bacteria53). Coumarins, isolated from a diverse group of marine organisms, including algae, fungi, and ascidians, also show antimicrobial activity54). Notably, coumarin has the potential to act as a quorum-sensing inhibitor by inhibiting the AI-2 activity of P. gingivalis55). Oroidin is a secondary metabolite of the marine sponge Agelas conifera that significantly reduces P. gingivalis biovolume56). These compounds reduced the expression of mfa1 and fimA in P. gingivalis, which encode the minor and major fimbrial subunits, respectively. These fimbrial adhesins are necessary for the co-adhesion between P. gingivalis and Streptococcus gordonii. These results demonstrate the potential of a small molecule inhibitor-based approach for preventing diseases associated with P. gingivalis56). Neoechinulin B is a natural marine product and a promising drug candidate for alleviating mortality and morbidity rates caused by drug-resistant infections57). Aurantoside K is a tetramic acid glycoside isolated from the Fijian marine sponge Melophlus that shows potent antifungal activity against wild-type and amphotericin-resistant C. albicans58).

3.Comparison with previous studies: new drug targets against oral pathogenic microorganisms

Recent studies have shown that oral microorganisms coexist and balance the oral environment of a healthy person. When the oral environment deteriorates, the composition and ratio of oral microorganisms change, and pathogenic microorganisms increase59-61). Many oral pathogenic microorganisms are anaerobic, whereas commensal non-pathogenic oral microorganisms are often aerobic bacteria62,63). An attempt has been made to develop a drug specific to oral pathogens using the difference in energy metabolism pathways between aerobic and anaerobic microorganisms by developing an inhibitor of a characteristic enzyme only present in anaerobic microorganisms. For example, treatment with amixicile (an inhibitor targeting pyruvate:ferredoxin oxidoreductase) inhibits oral pathogen growth, whereas aerobic oral bacteria are unaffected64,65). Additionally, it is possible to develop a specific drug targeting oral pathogenic microorganisms because the amino acid sequences of drug target proteins differ between oral pathogenic and non-pathogenic oral microorganisms66,67). For example, there is a large sequence difference between peptide deformylases in P. gingivalis and Streptococcus salivarius, with 28.3% sequence identity and 43.9% sequence homology (Table 3). Thus, it is possible to develop a peptide deformylase inhibitor that can inhibit the growth of P. gingivalis without inhibiting the growth of S. salivarius68).

Amino Acid Sequence Differences of Drug Development Target Protein in Various Oral Bacteria

Possible drug target protein in Porphyromonas gingivalis (UniProtKB code) Sequence identity/homology (UniProtKB code) with homologous protein
Streptococcus mutans Fusobacterium nucleatum Enterococcus faecalis Neisseria meningitidis Streptococcus salivarius
Methionine-tRNA ligase (Q7MXK7) 35.29%/53.07%
Peptide deformylase (Q7MT07) 29.36%/45.96%
Methionine Aminopeptidase (A0A134DR99) 38.89%/54.25%
Beta-ketoacyl-[acyl-carrier-protein] synthase III (Q7MAV3) 38.53%/60.91%
DNA gyrase subunit A (Q8L3L7) 47.77%/67.08%
DNA gyrase subunit B (A0A134DMA2) 55.57%/71.92%
DNA topoisomerase IV subunit A (A0A2D2N546) 27.48%/43.98%
N/A 28.63%/45.78%
DnaK (P0C937) 60.73%/72.36%
Peptidoglycan glycosyltransferase (A0A2D2NAU4) 27.65%/40.93%
1-Deoxy-D-xylulose-5-phosphate reductoisomerase (Q7MUW3) N/A 42.11%/62.44%
N/A 45.15%/63.35%
Superoxide dismutase [Mn/Fe] (P19665) 41.59%/54.67%
N/A 45.41%/57.49%
N/A 41.63%/54.55%
Aspartate semialdehyde dehydrogenase (A0A2D2N2E1) 46.60%/61.52%
Methylenetetrahydrofolate dehydrogenase/cyclohydrolase (Q7MVE9) 47.40%/64.29%
Riboflavin biosynthesis protein (Q7MWK9) N/A 53.10%/68.57%
Lumazine synthase (Q7MUR5) N/A 41.32%/60.48%
FAD synthetase (A0A2D2N1C2) 36.08%/54.26%

N/A means the sequence information is not available in the database.

When the number of pathogenic oral microorganisms increases, the expression of virulence factors and biofilm production is promoted through quorum sensing69-71). Recent studies have revealed the detailed mechanisms and functions of the genes involved in sensing oral pathogens. Biofilm formation induces antibiotic resistance in oral pathogenic microorganisms by inhibiting antibiotic penetration of antibiotics72,73). During biofilm formation, oral microorganisms are directly connected to each other through adhesion proteins and exchange various metabolites for signaling74-76). Fusobacterium nucleatum serves as a bridge between the early colonized microorganisms of the teeth and pathogenic microorganisms77,78). Following the discovery of quorum-sensing mechanisms and biofilm formation by oral pathogenic microorganisms, it is possible to develop antibacterial substances that only inhibit the growth of pathogens while preserving beneficial oral bacteria79,80). Substances that inhibit quorum sensing, biofilm formation, metabolite signaling, and direct interactions with oral pathogenic microorganisms are considered new drug candidates against oral pathogenic microorganisms (Table 4, 5)53,54,81-95).

Several Oral Pathogens have Quorum Sensing Systems

Oral pathogen Quorum sensing molecules Quorum sensing type Reference
Porphyromonas gingivalis Autoinducer-2 (AI-2) LuxS-encoded autoinducer (AI)-2 quorum sensing 83∼85
Prevotella intermedia Autoinducer-2 (AI-2) LuxS-encoded autoinducer (AI)-2 quorum sensing 84, 85
Fusobacterium nucleatum Autoinducer-2 (AI-2) LuxS-encoded autoinducer (AI)-2 quorum sensing 85, 86
Streptococcus mutans Autoinducer peptides (AIPs) ComD/ComE two-component-type quorum sensing 87
Competence-stimulating peptide (CSP)
Aggregatibacter actinomycetemcomitans Autoinducer-2 (AI-2) LuxS-encoded autoinducer (AI)-2 quorum sensing 88

Summary of Quorum Sensing Inhibitors Targeting Oral Pathogens

Quorum sensing inhibitor Inhibition target Mechanism of action Reference
Coumarin Porphyromonas gingivalis Inhibiting AI-2 activity 53, 54
Furanone compound
D-Ribose Fusobacterium nucleatum Inhibiting AI-2 activity and reducing biofilm formation 86, 89
P. gingivalis
Tannerella forsythia
D-Galactose F. nucleatum Preventing biofilm formation 90
Vibrio harveyi
P. gingivalis
T. forsythia
D-Arabinose F. nucleatum Inhibiting AI-2 activity 91
P. gingivalis
Streptococcus oralis
Short-chain fattyacids
(NaA, NaP, NaB, etc.)
Streptococcus gordonii Suppressing S. gordonii biofilm formation 92
Bicyclic brominated furanones P. gingivalis Inhibiting AI-2 activity without cytotoxicity or inflammatory response 93
F. nucleatum
T. forsythia
Baicalein Staphylococcus aureus Inhibiting biofilm formation and destruction 94
Streptococcus mutans
Furanone C-30 S. mutans Inhibiting biofilm formation in S. mutans and its lux S. mutant strain 95

4.Conclusion and suggestion

Rapid developments in molecular biology, genome analysis, and metabolite analysis technologies have enabled the identification of novel oral disease mechanisms in oral pathogens. Various signaling molecules and interacting proteins related to biofilm formation by certain oral pathogens have been identified. Proteins involved in the production of signaling molecules and signal transduction during biofilm formation can serve as new drug targets against oral pathogens. If drugs are developed to target proteins unique to oral pathogens, it would be possible to selectively eliminate oral pathogens, while preserving beneficial oral commensal microorganisms. Establishing a rapid and accurate activity measurement method for each new drug candidate target protein is also necessary. In conclusion, it is important to study the various mechanisms of action of oral pathogens and identify new target proteins to develop novel antibiotics against oral pathogens. In this review, we investigated six successful cases of confirmed antibacterial activity against oral pathogens using marine natural products. Most studies on the antibacterial activity of natural marine products have been conducted on general rather than oral pathogens. Therefore, it is necessary to investigate the application of substances with known antibacterial activities against oral pathogens. Moreover, it is important to screen for novel antibiotics in marine organisms to address the antibiotic resistance issues associated with oral diseases.



Conflict of interest

No potential conflict of interest relevant to this article was reported.

Ethical approval

Not applicable.

Author contributions

Conceptualization: Youn-Soo Shim and Jun Hyuck Lee. Data acquisition: Sehyeok Im. Formal analysis: Sehyeok Im. Funding: Jun Hyuck Lee. Supervision: Youn-Soo Shim and Jun Hyuck Lee. Writing-original draft: Sehyeok Im. Writing-review & editing: Youn-Soo Shim and Jun Hyuck Lee.


This research was supported by the project titled “Development of potential antibiotic compounds using polar organism resources (20200610, KOPRI Grant PM24030)”, funded by the Ministry of Oceans and Fisheries, Korea.

Data availability

Raw data is provided by the corresponding author upon reasonable request.

  1. Takahashi N: Oral microbiome metabolism: from "who are they?" to "what are they doing?". J Dent Res 94: 1628-1637, 2015.
    Pubmed CrossRef
  2. Xu X, He J, Xue J, et al.: Oral cavity contains distinct niches with dynamic microbial communities. Environ Microbiol 17: 699-710, 2015.
    Pubmed CrossRef
  3. Bowen WH, Burne RA, Wu H, Koo H: Oral biofilms: pathogens, matrix, and polymicrobial interactions in microenvironments. Trends Microbiol 26: 229-242, 2018.
    Pubmed KoreaMed CrossRef
  4. Marsh PD: Microbiology of dental plaque biofilms and their role in oral health and caries. Dent Clin North Am 54: 441-454, 2010.
    Pubmed CrossRef
  5. Marsh PD: Dental plaque as a biofilm and a microbial community - implications for health and disease. BMC Oral Health 6 Suppl 1: S14, 2006.
    Pubmed KoreaMed CrossRef
  6. Debelian GJ, Olsen I, Tronstad L: Systemic diseases caused by oral microorganisms. Endod Dent Traumatol 10: 57-65, 1994.
    Pubmed CrossRef
  7. Beck JD, Offenbacher S: Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease. J Periodontol 76: 2089-2100, 2005.
    Pubmed CrossRef
  8. Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ: Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Clin Periodontol 40: S135-S152, 2013.
    Pubmed CrossRef
  9. Olsen I, Yilmaz Ö: Possible role of Porphyromonas gingivalis in orodigestive cancers. J Oral Microbiol 11: 1563410, 2019.
    Pubmed KoreaMed CrossRef
  10. Könönen E, Fteita D, Gursoy UK, Gursoy M: Prevotella species as oral residents and infectious agents with potential impact on systemic conditions. J Oral Microbiol 14: 2079814, 2022.
    Pubmed KoreaMed CrossRef
  11. Issrani R, Reddy J, Dabah THE, et al.: Exploring the mechanisms and association between oral microflora and systemic diseases. Diagnostics (Basel) 12: 2800, 2022.
    Pubmed KoreaMed CrossRef
  12. Aas JA, Griffen AL, Dardis SR, et al.: Bacteria of dental caries in primary and permanent teeth in children and young adults. J Clin Microbiol 46: 1407-1417, 2008.
    Pubmed KoreaMed CrossRef
  13. Yanagisawa M, Kuriyama T, Williams DW, Nakagawa K, Karasawa T: Proteinase activity of Prevotella species associated with oral purulent infection. Curr Microbiol 52: 375-378, 2006.
    Pubmed CrossRef
  14. Neilands J, Wickström C, Kinnby B, et al.: Bacterial profiles and proteolytic activity in peri-implantitis versus healthy sites. Anaerobe 35: 28-34, 2015.
    Pubmed CrossRef
  15. van Winkelhoff AJ, Loos BG, van der Reijden WA, van der Velden U: Porphyromonas gingivalis, Bacteroides forsythus and other putative periodontal pathogens in subjects with and without periodontal destruction. J Clin Periodontol 29: 1023-1028, 2002.
    Pubmed CrossRef
  16. Bostanci N, Belibasakis GN: Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiol Lett 333: 1-9, 2012.
    Pubmed CrossRef
  17. Bao K, Belibasakis GN, Thurnheer T, Aduse-Opoku J, Curtis MA, Bostanci N: Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation. BMC Microbiol 14: 258, 2014.
    Pubmed KoreaMed CrossRef
  18. Scannapieco FA: Role of oral bacteria in respiratory infection. J Periodontol 70: 793-802, 1999.
    Pubmed CrossRef
  19. Williams D, Lewis M: Pathogenesis and treatment of oral candidosis. J Oral Microbiol 3: 5771, 2011.
    Pubmed KoreaMed CrossRef
  20. Vila T, Sultan AS, Montelongo-Jauregui D, Jabra-Rizk MA: Oral candidiasis: a disease of opportunity. J Fungi (Basel) 6: 15, 2020.
    Pubmed KoreaMed CrossRef
  21. Patil S, Rao RS, Sanketh DS, Amrutha N: Microbial flora in oral diseases. J Contemp Dent Pract 14: 1202-1208, 2013.
    Pubmed CrossRef
  22. Deepa A, Nair BJ, Sivakumar T, Joseph AP: Uncommon opportunistic fungal infections of oral cavity: a review. J Oral Maxillofac Pathol 18: 235-243, 2014.
    Pubmed KoreaMed CrossRef
  23. Seifert HS: Location, location, location-commensalism, damage and evolution of the pathogenic Neisseria. J Mol Biol 431: 3010-3014, 2019.
    Pubmed CrossRef
  24. Giacomini JJ, Torres-Morales J, Tang J, Dewhirst FE, Borisy GG, Mark Welch JL: Spatial ecology of Haemophilus and Aggregatibacter in the human oral cavity. Microbiol Spectr 12: e0401723, 2024.
    Pubmed KoreaMed CrossRef
  25. Jakubovics NS, Kolenbrander PE: The road to ruin: the formation of disease-associated oral biofilms. Oral Dis 16: 729-739, 2010.
    Pubmed CrossRef
  26. Kolenbrander PE, Palmer RJ Jr, Periasamy S, Jakubovics NS: Oral multispecies biofilm development and the key role of cell-cell distance. Nat Rev Microbiol 8: 471-480, 2010.
    Pubmed CrossRef
  27. Hasty DL, Ofek I, Courtney HS, Doyle RJ: Multiple adhesins of streptococci. Infect Immun 60: 2147-2152, 1992.
    Pubmed KoreaMed CrossRef
  28. Jakubovics NS, Kerrigan SW, Nobbs AH, et al.: Functions of cell surface-anchored antigen I/II family and Hsa polypeptides in interactions of Streptococcus gordonii with host receptors. Infect Immun 73: 6629-6638, 2005.
    Pubmed KoreaMed CrossRef
  29. Jakubovics NS, Strömberg N, van Dolleweerd CJ, Kelly CG, Jenkinson HF: Differential binding specificities of oral streptococcal antigen I/II family adhesins for human or bacterial ligands. Mol Microbiol 55: 1591-1605, 2005.
    Pubmed CrossRef
  30. Llor C, Bjerrum L: Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf 5: 229-241, 2014.
    Pubmed KoreaMed CrossRef
  31. Wright GD, Sutherland AD: New strategies for combating multidrug-resistant bacteria. Trends Mol Med 13: 260-267, 2007.
    Pubmed CrossRef
  32. Alonso A, Campanario E, Martínez JL: Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa. Microbiology 145: 2857-2862, 1999.
    Pubmed CrossRef
  33. Terreni M, Taccani M, Pregnolato M: New antibiotics for multidrug-resistant bacterial strains: latest research developments and future perspectives. Molecules 26: 2671, 2021.
    Pubmed KoreaMed CrossRef
  34. Brooks L, Narvekar U, McDonald A, Mullany P: Prevalence of antibiotic resistance genes in the oral cavity and mobile genetic elements that disseminate antimicrobial resistance: a systematic review. Mol Oral Microbiol 37: 133-153, 2022.
    Pubmed CrossRef
  35. Demain AL: Antibiotics: natural products essential to human health. Med Res Rev 29: 821-842, 2009.
    Pubmed CrossRef
  36. Demain AL: Importance of microbial natural products and the need to revitalize their discovery. J Ind Microbiol Biotechnol 41: 185-201, 2014.
    Pubmed CrossRef
  37. Moloney MG: Natural products as a source for novel antibiotics. Trends Pharmacol Sci 37: 689-701, 2016.
    Pubmed CrossRef
  38. Mehbub MF, Perkins MV, Zhang W, Franco CMM: New marine natural products from sponges (Porifera) of the order Dictyoceratida (2001 to 2012); a promising source for drug discovery, exploration and future prospects. Biotechnol Adv 34: 473-491, 2016.
    Pubmed CrossRef
  39. Stonik VA, Makarieva TN, Shubina LK: Antibiotics from marine bacteria. Biochemistry (Mosc) 85: 1362-1373, 2020.
    Pubmed CrossRef
  40. Fiedler HP, Bruntner C, Bull AT, et al.: Marine actinomycetes as a source of novel secondary metabolites. Antonie Van Leeuwenhoek 87: 37-42, 2005.
    Pubmed CrossRef
  41. Jagannathan SV, Manemann EM, Rowe SE, Callender MC, Soto W: Marine actinomycetes, new sources of biotechnological products. Mar Drugs 19: 365, 2021.
    Pubmed KoreaMed CrossRef
  42. Deng Y, Liu Y, Li J, et al.: Marine natural products and their synthetic analogs as promising antibiofilm agents for antibiotics discovery and development. Eur J Med Chem 239: 114513, 2022.
    Pubmed CrossRef
  43. Liu M, Liu Y, Cao MJ, et al.: Antibacterial activity and mechanisms of depolymerized fucoidans isolated from Laminaria japonica. Carbohydr Polym 172: 294-305, 2017.
    Pubmed CrossRef
  44. Oka S, Okabe M, Tsubura S, Mikami M, Imai A: Properties of fucoidans beneficial to oral healthcare. Odontology 108: 34-42, 2020.
    Pubmed CrossRef
  45. Senthilkumar K, Manivasagan P, Venkatesan J, Kim SK: Brown seaweed fucoidan: biological activity and apoptosis, growth signaling mechanism in cancer. Int J Biol Macromol 60: 366-374, 2013.
    Pubmed CrossRef
  46. Fitton JH: Therapies from fucoidan; multifunctional marine polymers. Mar Drugs 9: 1731-1760, 2011.
    Pubmed KoreaMed CrossRef
  47. de A, Lima B, de Lira SP, Kossuga MH, Gonçalves RB, Berlinck RGS, Kamiya RU: Halistanol sulfate A and rodriguesines A and B are antimicrobial and antibiofilm agents against the cariogenic bacterium Streptococcus mutans. Rev Bras Farmacogn 24: 651-659, 2014.
  48. Fusetani N, Matsunaga S, Konosu S: Bioactive marine metabolites II. Halistanol sulfate, an antimicrobial novel steroid sulfate from the marine sponge Halichondria cf. Moorei bergquist. Tetrahedron Lett 22: 1985-1988, 1981.
  49. Schneemann I, Kajahn I, Ohlendorf B, et al.: Mayamycin, a cytotoxic polyketide from a Streptomyces strain isolated from the marine sponge Halichondria panicea. J Nat Prod 73: 1309-1312, 2010.
    Pubmed CrossRef
  50. Matsuda S, Adachi K, Matsuo Y, Nukina M, Shizuri Y: Salinisporamycin, a novel metabolite from Salinispora arenicola. [corrected]. J Antibiot (Tokyo) 62: 519-526, 2009.
    Pubmed CrossRef
  51. Sabido EM, Tenebro CP, Suarez AFL, et al.: Marine sediment-derived Streptomyces strain produces angucycline antibiotics against multidrug-resistant Staphylococcus aureus harboring SCCmec type 1 gene. J Mar Sci Eng 8: 734, 2020.
  52. Radjasa OK, Salasia SIO, Sabdono A, et al.: Antibacterial activity of marine bacterium Pseudomonas sp. Associated with soft coral Sinularia polydactyla against Streptococcus equi subsp. Zooepidemicus. Int J Pharmacol 3: 170-174, 2007.
  53. Noga EJ, Stone KL, Wood A, Gordon WL, Robinette D: Primary structure and cellular localization of callinectin, an antimicrobial peptide from the blue crab. Dev Comp Immunol 35: 409-415, 2011.
    Pubmed KoreaMed CrossRef
  54. Fernández-Peña L, Matos MJ, López E: Recent advances in biologically active coumarins from marine sources: synthesis and evaluation. Mar Drugs 21: 37, 2023.
    Pubmed KoreaMed CrossRef
  55. He Z, Jiang W, Jiang Y, et al.: Anti-biofilm activities of coumarin as quorum sensing inhibitor for Porphyromonas gingivalis. J Oral Microbiol 14: 2055523, 2022.
    Pubmed KoreaMed CrossRef
  56. Wright CJ, Wu H, Melander RJ, Melander C, Lamont RJ: Disruption of heterotypic community development by Porphyromonas gingivalis with small molecule inhibitors. Mol Oral Microbiol 29: 185-193, 2014.
    Pubmed KoreaMed CrossRef
  57. Abdelmohsen UR, Balasubramanian S, Oelschlaeger TA, et al.: Potential of marine natural products against drug-resistant fungal, viral, and parasitic infections. Lancet Infect Dis 17: e30-e41, 2017.
    Pubmed CrossRef
  58. Kumar R, Subramani R, Feussner KD, Aalbersberg W: Aurantoside K, a new antifungal tetramic acid glycoside from a Fijian marine sponge of the genus Melophlus. Mar Drugs 10: 200-208, 2012.
    Pubmed KoreaMed CrossRef
  59. Sbordone L, Bortolaia C: Oral microbial biofilms and plaque-related diseases: microbial communities and their role in the shift from oral health to disease. Clin Oral Investig 7: 181-188, 2003.
    Pubmed CrossRef
  60. Kilian M: The oral microbiome - friend or foe? Eur J Oral Sci 126: 5-12, 2018.
    Pubmed CrossRef
  61. Sultan AS, Kong EF, Rizk AM, Jabra-Rizk MA: The oral microbiome: a lesson in coexistence. PLoS Pathog 14: e1006719, 2018.
    Pubmed KoreaMed CrossRef
  62. Dewhirst FE, Chen T, Izard J, et al.: The human oral microbiome. J Bacteriol 192: 5002-5017, 2010.
    Pubmed KoreaMed CrossRef
  63. Baty JJ, Stoner SN, Scoffield JA: Oral commensal streptococci: gatekeepers of the oral cavity. J Bacteriol 204: e0025722, 2022.
    Pubmed KoreaMed CrossRef
  64. Hutcherson JA, Sinclair KM, Belvin BR, Gui Q, Hoffman PS, Lewis JP: Amixicile, a novel strategy for targeting oral anaerobic pathogens. Sci Rep 7: 10474, 2017.
    Pubmed KoreaMed CrossRef
  65. Gui Q, Hoffman PS, Lewis JP: Amixicile targets anaerobic bacteria within the oral microbiome. J Oral Biosci 61: 226-235, 2019.
    Pubmed KoreaMed CrossRef
  66. Pérot S, Sperandio O, Miteva MA, Camproux AC, Villoutreix BO: Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery. Drug Discov Today 15: 656-667, 2010.
    Pubmed CrossRef
  67. Stone VN, Xu P: Targeted antimicrobial therapy in the microbiome era. Mol Oral Microbiol 32: 446-454, 2017.
    Pubmed KoreaMed CrossRef
  68. Soga S, Shirai H, Kobori M, Hirayama N: Use of amino acid composition to predict ligand-binding sites. J Chem Inf Model 47: 400-406, 2007.
    Pubmed CrossRef
  69. Fuqua WC, Winans SC, Greenberg EP: Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 176: 269-275, 1994.
    Pubmed KoreaMed CrossRef
  70. Shao H, Demuth DR: Quorum sensing regulation of biofilm growth and gene expression by oral bacteria and periodontal pathogens. Periodontol 2000 52: 53-67, 2010.
    Pubmed CrossRef
  71. Niazy AA: LuxS quorum sensing system and biofilm formation of oral microflora: a short review article. Saudi Dent J 33: 116-123, 2021.
    Pubmed KoreaMed CrossRef
  72. Stewart PS, Costerton JW: Antibiotic resistance of bacteria in biofilms. Lancet 358: 135-138, 2001.
    Pubmed CrossRef
  73. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O: Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 35: 322-332, 2010.
    Pubmed CrossRef
  74. Jenkinson HF, Demuth DR: Structure, function and immunogenicity of streptococcal antigen I/II polypeptides. Mol Microbiol 23: 183-190, 1997.
    Pubmed CrossRef
  75. Ahn SJ, Ahn SJ, Wen ZT, Brady LJ, Burne RA: Characteristics of biofilm formation by Streptococcus mutans in the presence of saliva. Infect Immun 76: 4259-4268, 2008.
    Pubmed KoreaMed CrossRef
  76. Arciola CR, Campoccia D, Ravaioli S, Montanaro L: Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects. Front Cell Infect Microbiol 5: 7, 2015.
    Pubmed KoreaMed CrossRef
  77. Sharma A, Inagaki S, Sigurdson W, Kuramitsu HK: Synergy between Tannerella forsythia and Fusobacterium nucleatum in biofilm formation. Oral Microbiol Immunol 20: 39-42, 2005.
    Pubmed CrossRef
  78. Okuda T, Kokubu E, Kawana T, Saito A, Okuda K, Ishihara K: Synergy in biofilm formation between Fusobacterium nucleatum and Prevotella species. Anaerobe 18: 110-116, 2012.
    Pubmed CrossRef
  79. Sarangi AN, Aggarwal R, Rahman A, Trivedi N: Subtractive genomics approach for in silico identification and characterization of novel drug targets in Neisseria meningitides serogroup B. J Comput Sci Syst Biol 2: 255-258, 2009.
  80. Gerits E, Verstraeten N, Michiels J: New approaches to combat Porphyromonas gingivalis biofilms. J Oral Microbiol 9: 1300366, 2017.
    Pubmed KoreaMed CrossRef
  81. Rasmussen TB, Givskov M: Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296: 149-161, 2006.
    Pubmed CrossRef
  82. Haque S, Ahmad F, Dar SA, et al.: Developments in strategies for quorum sensing virulence factor inhibition to combat bacterial drug resistance. Microb Pathog 121: 293-302, 2018.
    Pubmed CrossRef
  83. Chung WO, Park Y, Lamont RJ, McNab R, Barbieri B, Demuth DR: Signaling system in Porphyromonas gingivalis based on a LuxS protein. J Bacteriol 183: 3903-3909, 2001.
    Pubmed KoreaMed CrossRef
  84. Frias J, Olle E, Alsina M: Periodontal pathogens produce quorum sensing signal molecules. Infect Immun 69: 3431-3434, 2001.
    Pubmed KoreaMed CrossRef
  85. Kolenbrander PE, Palmer RJ Jr, Rickard AH, Jakubovics NS, Chalmers NI, Diaz PI: Bacterial interactions and successions during plaque development. Periodontol 2000 42: 47-79, 2006.
    Pubmed CrossRef
  86. Jang YJ, Choi YJ, Lee SH, Jun HK, Choi BK: Autoinducer 2 of Fusobacterium nucleatum as a target molecule to inhibit biofilm formation of periodontopathogens. Arch Oral Biol 58: 17-27, 2013.
    Pubmed CrossRef
  87. Senadheera D, Cvitkovitch DG: Quorum sensing and biofilm formation by Streptococcus mutans. Adv Exp Med Biol 631: 178-188, 2008.
    Pubmed CrossRef
  88. Shao H, Lamont RJ, Demuth DR: Autoinducer 2 is required for biofilm growth of Aggregatibacter (Actinobacillus) actinomycetemcomitans. Infect Immun 75: 4211-4218, 2007.
    Pubmed KoreaMed CrossRef
  89. Cho YJ, Song HY, Ben Amara H, et al.: In vivo inhibition of Porphyromonas gingivalis growth and prevention of periodontitis with quorum-sensing inhibitors. J Periodontol 87: 1075-1082, 2016.
    Pubmed CrossRef
  90. Ryu EJ, Sim J, Sim J, Lee J, Choi BK: D-galactose as an autoinducer 2 inhibitor to control the biofilm formation of periodontopathogens. J Microbiol 54: 632-637, 2016.
    Pubmed CrossRef
  91. An SJ, Namkung JU, Ha KW, Jun HK, Kim HY, Choi BK: Inhibitory effect of D-arabinose on oral bacteria biofilm formation on titanium discs. Anaerobe 75: 102533, 2022.
    Pubmed CrossRef
  92. Park T, Im J, Kim AR, et al.: Short-chain fatty acids inhibit the biofilm formation of Streptococcus gordonii through negative regulation of competence-stimulating peptide signaling pathway. J Microbiol 59: 1142-1149, 2021.
    Pubmed CrossRef
  93. Park JS, Ryu EJ, Li L, Choi BK, Kim BM: New bicyclic brominated furanones as potent autoinducer-2 quorum-sensing inhibitors against bacterial biofilm formation. Eur J Med Chem 137: 76-87, 2017.
    Pubmed CrossRef
  94. Chen Y, Liu T, Wang K, et al.: Baicalein inhibits Staphylococcus aureus biofilm formation and the quorum sensing system in vitro. PLoS One 11: e0153468, 2016.
    Pubmed KoreaMed CrossRef
  95. He Z, Wang Q, Hu Y, et al.: Use of the quorum sensing inhibitor furanone C-30 to interfere with biofilm formation by Streptococcus mutans and its luxS mutant strain. Int J Antimicrob Agents 40: 30-35, 2012.
    Pubmed CrossRef

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