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Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm

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

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 22068

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Prof. Dr. María C. Sánchez Beltrán

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Department of Medicine, Faculty of Medicine, University Complutense of Madrid, Madrid, Spain
Interests: microbiology; bacterial biofilms; oral pathogens; genomics; metabolomics; cell biology; development of new antimicrobial agents; mechanisms of antibiotic resistance
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Sigrun Eick

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Guest Editor

Department of Periodontology, Laboratory of Oral Microbiology, School of Dental Medicine, University of Bern, Bern, Switzerland
Interests: antimicrobial therapy in dentistry; biofilms; antibiotics; alternatives to antibiotics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the oral cavity, microbial homeostasis and its maintenance represent a major global challenge. The alteration of the balance in the oral cavity, and, therefore, the dysbiosis of the microbial community present in its different locations, constitute an important factor in determining the virulence of a microbial consortium of multiple species and the consequent development of oral infectious diseases, including dental caries, gingivitis, periodontitis, endodontic periapical lesions, and peri-implantitis.

The effective management of biofilm-related oral infectious diseases is a challenge with multiple approaches, from the precise and continuous elimination of specific oral pathogens to the use of antimicrobial agent release, contact-killing, and multi-functional strategies for the prevention of initial bacterial attachment or biofilm dispersal. Likewise, it includes the use of probiotics and compounds modulating the virulence of the oral biofilm without killing commensal bacteria or the application of novel approach as nanomaterials, quaternary ammonium salts, small molecules, arginine, and natural products, avoiding the elimination of commensals that can cause ecological dysbiosis. Antimicrobial photodynamic therapy or cold atmospheric plasma application has also emerged as an alternative to antimicrobial treatments and biofilm disruption.

This Special Issue aims to gather papers describing innovative antimicrobial strategies with the potential to control infections related to oral biofilms with special interest in those capable of inhibiting biofilm virulence without necessarily inducing the microbial dysbiosis of oral biofilms. These methods can be used in the near future to effectively promote the clinical management of infectious oral diseases and thus benefit oral health in the face of the increasing emergence of antibiotic-resistant bacteria.

Articles that address the wide variety of issues in antimicrobial strategies and infection control are welcome. We kindly invite you to submit original research articles as well as review articles. All articles will be peer reviewed.

Prof. Dr. María C. Sánchez Beltrán
Prof. Dr. Sigrun Eick
Guest Editors

Manuscript Submission Information

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

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

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

Keywords

oral biofilms
oral pathogenic bacteria
oral infections
antimicrobial strategies
microbial oral homeostasis
oral dysbiosis
antibiotic resistance

Related Special Issue

Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm—2nd Volume in Antibiotics (1 article)

Published Papers (9 papers)

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Research

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15 pages, 1672 KiB

Open AccessArticle

Antibiotic Resistance of Selected Bacteria after Treatment of the Supragingival Biofilm with Subinhibitory Chlorhexidine Concentrations

by Robin Früh, Annette Anderson, Fabian Cieplik, Elmar Hellwig, Annette Wittmer, Kirstin Vach and Ali Al-Ahmad

Antibiotics 2022, 11(10), 1420; https://doi.org/10.3390/antibiotics11101420 - 17 Oct 2022

Cited by 2 | Viewed by 1372

Abstract

Due to increasing rates of antibiotic resistance and very few novel developments of antibiotics, it is crucial to understand the mechanisms of resistance development. The aim of the present study was to investigate the adaptation of oral bacteria to the frequently used oral antiseptic chlorhexidine digluconate (CHX) and potential cross-adaptation to antibiotics after repeated exposure of supragingival plaque samples to subinhibitory concentrations of CHX. Plaque samples from six healthy donors were passaged for 10 days in subinhibitory concentrations of CHX, while passaging of plaque samples without CHX served as control. The surviving bacteria were cultured on agar plates and identified with Matrix-assisted Laser Desorption/Ionization-Time of Flight-Mass spectrometry (MALDI-TOF). Subsequently, the minimum inhibitory concentrations (MIC) of these isolates toward CHX were determined using a broth-microdilution method, and phenotypic antibiotic resistance was evaluated using the epsilometertest. Furthermore, biofilm-forming capacities were determined. Repeated exposure of supragingival plaque samples to subinhibitory concentrations of CHX led to the selection of oral bacteria with 2-fold up to 4-fold increased MICs toward CHX. Furthermore, these isolates showed up to 12-fold increased MICs towards some antibiotics such as erythromycin and clindamycin. Conversely, biofilm-forming capacity was decreased. In summary, this study shows that oral bacteria are able to adapt to CHX, while also decreasing their susceptibility to antibiotics. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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16 pages, 1927 KiB

Open AccessArticle

Dental Biofilm Removal and Bacterial Contamination of a New Doubled-Side Thermoplastic Polyurethane-Based Toothbrush: A Crossover Study in Healthy Volunteers

by Ignacio Zúñiga, Margarita Iniesta, Leire Virto, Honorato Ribeiro-Vidal, Andrea Alonso-Español, Fernando Hernández, John Jairo Cardona, Anushiravan Maher-Lavandero, Bettina Alonso, Mariano Sanz and David Herrera

Antibiotics 2022, 11(10), 1296; https://doi.org/10.3390/antibiotics11101296 - 22 Sep 2022

Cited by 2 | Viewed by 2523

Abstract

Multiple toothbrush designs have been developed to enhance dental biofilm removal and decrease bacterial contamination and retention over time. Therefore, the aim of this clinical study was to compare the efficacy of a prototype of a new double-sided thermoplastic polyurethane-based toothbrush with that of a conventional nylon-bristle toothbrush. A crossover study was conducted in systemically healthy volunteers (n = 24) for two one-week periods plus one washout week. As outcome variables, plaque and gingival indices, total bacterial contamination of the toothbrushes by quantitative polymerase chain reaction (qPCR), and patient-reported outcomes were measured. Clinical and microbiological variables were analysed using a general linear model and Friedman and Wilcoxon signed-rank tests. No statistically significant differences between toothbrushes were detected neither for full-mouth PlI (p > 0.05) nor for GI (p > 0.05). Similarly, no statistically significant differences were detected for bacterial contamination after 40 seconds or 1 week of use, with results expressed either in CFU/mL or in CFU/mm² (p > 0.05). In conclusion, the tested prototype toothbrush was as effective and safe as the control toothbrush, and the participating subjects did not experience any adverse effects from its use and rated its efficiency and effectiveness in cleaning their teeth as satisfactory. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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11 pages, 785 KiB

Open AccessArticle

Antibiotic Susceptibility and Resistance Genes in Oral Clinical Isolates of Prevotella intermedia, Prevotella nigrescens, and Prevotella melaninogenica

by Yormaris Castillo, Nathaly Andrea Delgadillo, Yineth Neuta, Andrés Hernández, Tania Acevedo, Edwin Cárdenas, Andrea Montaño, Gloria Inés Lafaurie and Diana Marcela Castillo

Antibiotics 2022, 11(7), 888; https://doi.org/10.3390/antibiotics11070888 - 04 Jul 2022

Cited by 4 | Viewed by 2647

Abstract

The Prevotella genus is a normal constituent of the oral microbiota, and is commonly isolated from mechanically treated polymicrobial infections. However, antibiotic treatment is necessary for some patients. This study compared the antibiotic susceptibility and the presence of resistance genes in clinical oral isolates of P. intermedia, P. nigrescens, and P. melaninogenica. Antibiotic susceptibility was assessed using the agar dilution method. PCR confirmed the species and resistance gene frequency in the Prevotella species. The frequencies of species P. intermedia, P. nigrescens, and P. melaninogenica were 30.2%, 45.7%, and 24.1%, respectively. No isolates of P. intermedia were resistant to amoxicillin/clavulanic acid, tetracycline, or clindamycin. P. nigrescens and P. melaninogenica were resistant to amoxicillin/clavulanic acid and tetracycline at frequencies of 40% and 20%, respectively. P. intermedia was resistant to metronidazole at a frequency of 30%, P. nigrescens at 20%, and P. melaninogenica at 40%. P. nigrescens and P. melaninogenica were resistant to 50% and 10% clindamycin, respectively. The gene most frequently detected was tetQ, at 43.3%, followed by tetM at 36.6%, bla_TEM at 26.6%, ermF at 20%, cfxA, cfxA₂, and nimAB at 16.6%, and nimAEFI at 3.3%. P. nigrescens was the species with the highest resistance to antibiotics such as amoxicillin/clavulanic acid, amoxicillin, and clindamycin, in addition to being the species with the largest number of genes compared to P. intermedia and P. melaninogenica. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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12 pages, 2581 KiB

Open AccessArticle

Antibacterial and Anti-Inflammatory Properties of a Novel Antimicrobial Peptide Derived from LL-37

by Haiwei Zhuo, Xi Zhang, Maogen Li, Qian Zhang and Yonglan Wang

Antibiotics 2022, 11(6), 754; https://doi.org/10.3390/antibiotics11060754 - 01 Jun 2022

Cited by 4 | Viewed by 2500

Abstract

Peri-implantitis is a pathological condition involving tissues around dental implants that are characterized by inflammation of the peri-implant mucosa and progressive loss of supporting bone. We found that the antimicrobial peptide KR-12-3 (KRIVKWIKKFLR) derived from LL-37 had antibacterial properties against Streptococcus gordonii. The purpose of this study was to evaluate its antibacterial and anti-inflammatory activities and its underlying mechanisms. We evaluated the antibacterial activities of antimicrobial peptides in planktonic and biofilm states by measuring their minimum inhibitory concentration, minimum bactericidal concentration, and biofilm susceptibility. The effects of antimicrobial peptides on the production of IL-6 and IL-8 in LPS-stimulated RAW264.7 cells were detected by enzyme-linked immunosorbent assay and other experiments, and their toxicity to MC3T3-E1 cells was also studied. While maintaining low cytotoxicity, KR-12-3 exhibited growth inhibitory effects on S. gordonii in planktonic and biofilm states. Lower concentrations of KR-12-3 treatment reduced the production of inflammatory cytokines in LPS-stimulated RAW264.8 cells. The mechanisms underlying the inhibition of biofilm formation and anti-inflammatory effects have been associated with the low expression of related genes. KR-12-3 may be used to develop an antibacterial, anti-infective, and anti-inflammatory drugs for peri-implantitis. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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14 pages, 2011 KiB

Open AccessArticle

The In-Vitro Activity of a Cold Atmospheric Plasma Device Utilizing Ambient Air against Bacteria and Biofilms Associated with Periodontal or Peri-Implant Diseases

by Gert Jungbauer, Leandro Favaro, Steffen Müller, Anton Sculean and Sigrun Eick

Antibiotics 2022, 11(6), 752; https://doi.org/10.3390/antibiotics11060752 - 31 May 2022

Cited by 10 | Viewed by 2387

Abstract

Due to its antimicrobial and healing-promoting effects, the application of cold atmospheric plasma (CAP) appears to be a promising modality in various fields of general medicine and dentistry. The aim of the present study was to evaluate the antibacterial and anti-biofilm activity of a handheld device utilizing ambient air for plasma generation. Suspensions of 11 oral bacteria (among them Fusobacterium nucleatum, Porphyromonas gingivalis, Parvimonas micra, Streptococcus gordonii, and Tannerella forsythia) were exposed to CAP for 10, 30, 60, and 120 s. Before and after treatment, colony forming unit (CFU) counts were determined. Then, 12-species biofilms were cultured on dentin and titanium specimens, and CAP was applied for 30, 60, and 120 s before quantifying CFU counts, biofilm mass, and metabolic activity. A reduction of ≥3 log₁₀ CFU, was found for ten out of the eleven tested species at 30 s (except for T. forsythia) and for all species at 60 s. For biofilm grown on dentin and titanium specimens, the log₁₀ reductions were 2.43 log₁₀ CFU/specimen and by about 4 log₁₀ CFU/specimen after 120 s of CAP. The CAP application did not reduce the biomass significantly, the metabolic activity of the biofilms on dentin and titanium decreased by 98% and 95% after 120 s of CAP. An application of 120 s of CAP had no cytotoxic effect on gingival fibroblasts and significantly increased the adhesion of gingival fibroblasts to the titanium surface. These results are promising and underline the potential of CAP for implementation in periodontal and peri-implantitis therapy. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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18 pages, 662 KiB

Open AccessArticle

Phenotypic Adaptation to Antiseptics and Effects on Biofilm Formation Capacity and Antibiotic Resistance in Clinical Isolates of Early Colonizers in Dental Plaque

by David L. Auer, Xiaojun Mao, Annette Carola Anderson, Denise Muehler, Annette Wittmer, Christiane von Ohle, Diana Wolff, Cornelia Frese, Karl-Anton Hiller, Tim Maisch, Wolfgang Buchalla, Elmar Hellwig, Ali Al-Ahmad and Fabian Cieplik

Antibiotics 2022, 11(5), 688; https://doi.org/10.3390/antibiotics11050688 - 19 May 2022

Cited by 10 | Viewed by 2255

Abstract

Despite the wide-spread use of antiseptics in dental practice and oral care products, there is little public awareness of potential risks associated with antiseptic resistance and potentially concomitant cross-resistance. Therefore, the aim of this study was to investigate potential phenotypic adaptation in 177 clinical isolates of early colonizers of dental plaque (Streptococcus, Actinomyces, Rothia and Veillonella spp.) upon repeated exposure to subinhibitory concentrations of chlorhexidine digluconate (CHX) or cetylpyridinium chloride (CPC) over 10 passages using a modified microdilution method. Stability of phenotypic adaptation was re-evaluated after culture in antiseptic-free nutrient broth for 24 or 72 h. Strains showing 8-fold minimal inhibitory concentration (MIC)-increase were further examined regarding their biofilm formation capacity, phenotypic antibiotic resistance and presence of antibiotic resistance genes (ARGs). Eight-fold MIC-increases to CHX were detected in four Streptococcus isolates. These strains mostly exhibited significantly increased biofilm formation capacity compared to their respective wild-type strains. Phenotypic antibiotic resistance was detected to tetracycline and erythromycin, consistent with the detected ARGs. In conclusion, this study shows that clinical isolates of early colonizers of dental plaque can phenotypically adapt toward antiseptics such as CHX upon repeated exposure. The underlying mechanisms at genomic and transcriptomic levels need to be investigated in future studies. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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14 pages, 3087 KiB

Open AccessArticle

The Effect of Toothpastes Containing Natural Extracts on Bacterial Species of a Microcosm Biofilm and on Enamel Caries Development

by Aline Silva Braga, Mohamed Mostafa Hefny Abdelbary, Rafaela Ricci Kim, Fernanda Pereira de Souza Rosa de Melo, Luiz Leonardo Saldanha, Anne Lígia Dokkedal, Georg Conrads, Marcella Esteves-Oliveira and Ana Carolina Magalhães

Antibiotics 2022, 11(3), 414; https://doi.org/10.3390/antibiotics11030414 - 19 Mar 2022

Cited by 6 | Viewed by 3093

Abstract

This study investigated the effects of herbal toothpaste on bacterial counts and enamel demineralization. Thirty-six bovine enamel samples were exposed to a microcosm biofilm using human saliva and McBain saliva (0.2% sucrose) for 5 days at 37 °C and first incubated anaerobically, then aerobically–capnophilically. The following experimental toothpaste slurries (2 × 2 min/day) were applied: (1) Vochysia tucanorum (10 mg/g); (2) Myrcia bella (5 mg/g); (3) Matricaria chamomilla (80 mg/g); (4) Myrrha and propolis toothpaste (commercial); (5) fluoride (F) and triclosan (1450 ppm F), 0.3% triclosan and sorbitol (Colgate^®, positive control); (6) placebo (negative control). The pH of the medium was measured, bacteria were analyzed using quantitative polymerase chain reaction, and enamel demineralization was quantified using transverse microradiography. The total bacterial count was reduced by toothpaste containing Myrcia bella, Matricaria chamomilla, fluoride, and triclosan (commercial) compared to the placebo. As far as assessable, Myrcia bella, Matricaria chamomilla, and Myrrha and propolis (commercial) inhibited the outgrowth of S. mutans, while Lactobacillus spp. were reduced/eliminated by all toothpastes except Vochysia tucanorum. Mineral loss and lesion depth were significantly reduced by all toothpastes (total: 1423.6 ± 115.2 vol% × μm; 57.3 ± 9.8 μm) compared to the placebo (2420.0 ± 626.0 vol% × μm; 108.9 ± 21.17 μm). Herbal toothpastes were able to reduce enamel demineralization. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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Review

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17 pages, 1005 KiB

Open AccessReview

Strategies to Combat Caries by Maintaining the Integrity of Biofilm and Homeostasis during the Rapid Phase of Supragingival Plaque Formation

by Paola Hernández, María C. Sánchez, Arancha Llama-Palacios, María J. Ciudad and Luis Collado

Antibiotics 2022, 11(7), 880; https://doi.org/10.3390/antibiotics11070880 - 30 Jun 2022

Cited by 12 | Viewed by 2776

Abstract

Bacteria in the oral cavity, including commensals and opportunistic pathogens, are organized into highly specialized sessile communities, coexisting in homeostasis with the host under healthy conditions. A dysbiotic environment during biofilm evolution, however, allows opportunistic pathogens to become the dominant species at caries-affected sites at the expense of health-associated taxa. Combining tooth brushing with dentifrices or rinses combat the onset of caries by partially removes plaque, but resulting in the biofilm remaining in an immature state with undesirables’ consequences on homeostasis and oral ecosystem. This leads to the need for therapeutic pathways that focus on preserving balance in the oral microbiota and applying strategies to combat caries by maintaining biofilm integrity and homeostasis during the rapid phase of supragingival plaque formation. Adhesion, nutrition, and communication are fundamental in this phase in which the bacteria that have survived these adverse conditions rebuild and reorganize the biofilm, and are considered targets for designing preventive strategies to guide the biofilm towards a composition compatible with health. The present review summarizes the most important advances and future prospects for therapies based on the maintenance of biofilm integrity and homeostasis as a preventive measure of dysbiosis focused on these three key factors during the rapid phase of plaque formation. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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14 pages, 2492 KiB

Open AccessCase Report

Analysis of the Oral Microbiome in a Patient with Cardiofaciocutaneous Syndrome and Severe Periodontal Disease: Impact of Systemic Antibiotic Therapy

by Carolina Muñoz Navarro, María del Carmen Sánchez Beltrán, Carolina Arriagada Vargas, Pilar Batalla Vázquez, Márcio Diniz Freitas, Jacobo Limeres Posse, Pedro Diz Dios and Eliane García Mato

Antibiotics 2022, 11(12), 1754; https://doi.org/10.3390/antibiotics11121754 - 04 Dec 2022

Cited by 3 | Viewed by 1592

Abstract

An 8-year-old girl diagnosed with cardiofaciocutaneous syndrome presented to our department with gingival pain, inflammation, and bleeding. Her medical history included hypoplasia of the corpus callosum, intellectual disability, trichothiodystrophy, global developmental delay, myopia, laryngomalacia, hypothyroidism, and osteoporosis. A diagnosis was reached of “periodontitis as a direct manifestation of systemic diseases”. During 9 years of follow-up, there were exacerbation episodes with spontaneous gum bleeding, ulcers in the interdental papilla, tooth mobility, and progressive tooth loss. Some of these exacerbation episodes resolved clinically with the administration of amoxicillin and metronidazole. We therefore proposed an oral microbiome study (subgingival and saliva samples) before and after antibiotic therapy. The most abundant genera at the subgingival level before administering antibiotics were Prevotella, Streptococcus, Fusobacterium, Leptotrichia, and Aggregatibacter. Of the 94 genera sequenced, 57 were less abundant in the post-treatment state than at baseline, particularly certain Gram-negative periodontal pathogens such as Porphyromonas, Treponema, Aggregatibacter, Fusobacterium, and Campylobacter. In contrast, other genera related to oral health, such as Haemophilus, Granulicatella, and Abiotrophia, showed an increase after administering the antibiotic. In conclusion, periodontitis exacerbations as a direct manifestation of systemic disease can occasionally be controlled exclusively with systemic antibiotics, without the need for performing mechanical periodontal therapy. This clinical recovery is correlated to substantial changes in the oral microbiome, which lead to the recovery of eubiosis of the microbiota. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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