Opportunistic Oral Pathogens in Oral and Systemic Diseases

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 24702

Special Issue Editors


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Guest Editor
Faculdade de Medicina Dentária, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
Interests: oral microbiome; human microbiome in health and disease; microbiome acquisition

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Guest Editor
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
Interests: oral microbiome; oral mycobiome; preventive dentistry

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Guest Editor
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
Interests: human microbiome; pathogens and opportunistic bacteria; antimicrobial resistance/tolerance; molecular epidemiology; microbial typing methods
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The oral microbiome encompasses the diverse community of bacteria, viruses, archaea, fungi, and protozoa that inhabit multiple niches of the oral cavity. The oral microorganisms and their inevitable inter-relationships are essential components in the balance between health and disease, both locally and systemically. The majority of the oral microorganisms are non-pathogenic opportunistic commensals, and they defend the oral ecosystem against pathogenic microorganisms. However, when there is an imbalance in oral homeostasis, i.e., oral dysbiosis, the microenvironment changes and allows opportunistic and potential pathogenic microorganisms to thrive and cause infections. Oral pathogens are currently recognized in the pathogenesis of several oral diseases, such as dental caries, periodontal diseases, endodontic infections, and also oral cancer. Moreover, the spread of oral microorganisms to other body sites, namely through a direct way, via hematogenous translocation or aspiration of oral pathogenic microorganisms or byproducts, and indirectly, through the release of inflammatory mediators to the bloodstream, may be associated with the emergence (or worsening) of systemic conditions, such as extra-oral infections, cancer, cardiovascular, and neurological and metabolic diseases. Since the oral cavity represents an important reservoir for pathogenic microorganisms, the study of the underlying mechanisms of pathogenicity of these microorganisms and their impact on oral and systemic homeostasis is of utmost importance.

Therefore, this Special Issue aims to update the knowledge on oral pathogens, particularly regarding their mechanisms for oral colonization, their pathogenicity, virulence and antimicrobial susceptibility, factors that impact their colonization in extra-oral sites, the interactions of oral pathogens with other microorganisms in oral and systemic biofilms, and their involvement in the underlying pathophysiologic mechanisms of oral and systemic diseases. Finally, this Special Issue also seeks to share recent strategies to detect colonization by oral pathogens and to contribute to the early diagnosis of infections, since it will be a key factor to control and prevent disease progression.

Dr. Benedita Sampaio-Maia
Dr. Maria João Azevedo
Dr. Joana Campos
Guest Editors

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Keywords

  • Oral pathogens
  • Oral diseases
  • Oral
  • Biofilms
  • Extra-oral infections
  • Systemic diseases linked to oral microbiome
  • Antimicrobial susceptibility of oral microbiota
  • Virulence factors of oral pathogens
  • Pathophysiologic mechanisms of oral pathogens
  • Diagnosis

Published Papers (8 papers)

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Research

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18 pages, 4579 KiB  
Article
Differential Modulation of Saliva-Derived Microcosm Biofilms by Antimicrobial Peptide LL-31 and D-LL-31
by Kahena R. Soldati, Yaling Jiang, Bernd W. Brandt, Rob A. M. Exterkate, Mark J. Buijs, Kamran Nazmi, Wendy E. Kaman, Lei Cheng, Floris J. Bikker, Wim Crielaard, Daniela L. Zandim-Barcelos and Dong Mei Deng
Pathogens 2023, 12(11), 1295; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12111295 - 29 Oct 2023
Viewed by 1000
Abstract
Microbiome modulation, aiming to restore a health-compatible microbiota, is a novel strategy to treat periodontitis. This study evaluated the modulation effects of antimicrobial peptide LL-31 and its D-enantiomer (D-LL-31) on saliva-derived microcosm biofilms, spiked with or without Porphyromonas gingivalis. To this end, [...] Read more.
Microbiome modulation, aiming to restore a health-compatible microbiota, is a novel strategy to treat periodontitis. This study evaluated the modulation effects of antimicrobial peptide LL-31 and its D-enantiomer (D-LL-31) on saliva-derived microcosm biofilms, spiked with or without Porphyromonas gingivalis. To this end, one-day-old biofilms were incubated for 24 h with biofilm medium alone, or medium containing 40 µM LL-31 or D-LL-31, after which biofilms were grown for 5 days. Biofilms were assessed at 1 day and 5 days after intervention for the total viable cell counts, dipeptidyl peptidase IV (DPP4) activity, P. gingivalis amount (by qPCR) and microbial composition (by sequencing). The results showed that D-LL-31, not LL-31, significantly reduced the total viable cell counts, the P. gingivalis amount, and the DPP4 activity of the biofilms spiked with P. gingivalis, but only at 1 day after intervention. In the biofilms spiked with P. gingivalis, D-LL-31 tended to reduce the α-diversity and the compositional shift of the biofilms in time as compared to the control and LL-31 groups. In conclusion, D-LL-31 showed a better performance than LL-31 in biofilm modulation. The biofilm modulation function of the peptides could be impaired when the biofilms were in a severely dysbiotic state. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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10 pages, 1005 KiB  
Article
Unveiling the Relevance of the Oral Cavity as a Staphylococcus aureus Colonization Site and Potential Source of Antimicrobial Resistance
by Joana Campos, Mariana Faria Pires, Marta Sousa, Carla Campos, Carolina Fernandes Ferreira Alves da Costa and Benedita Sampaio-Maia
Pathogens 2023, 12(6), 765; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12060765 - 26 May 2023
Cited by 2 | Viewed by 1933
Abstract
Staphylococcus aureus is both a human commensal and a pathogen, that causes serious nosocomial and community-acquired infections. Despite nostrils being considered its preferred host habitat, the oral cavity has been demonstrated to be an ideal starting point for auto-infection and transmission. The antibiotic [...] Read more.
Staphylococcus aureus is both a human commensal and a pathogen, that causes serious nosocomial and community-acquired infections. Despite nostrils being considered its preferred host habitat, the oral cavity has been demonstrated to be an ideal starting point for auto-infection and transmission. The antibiotic resistance assessment of S. aureus is a priority and is often reported in clinical settings. This study aimed to explore the prevalence and antimicrobial susceptibility of S. aureus in the oral and nasal cavities of healthy individuals. The participants (n = 101) were subjected to a demographic and clinical background survey, a caries evaluation, and to oral and nasal swabbing. Swabs were cultured in differential/selective media and S. aureus isolates were identified (MALDI-TOF MS) and tested for antibiotic susceptibility (EUCAST/CLSI). Similar S. aureus prevalence was found exclusively on nasal (13.9%) or oral (12.0%) habitats, whereas 9.9% of the population were simultaneous nasal and oral carriers. In oro-nasal cavities, similar antibiotic resistance rates (83.3–81.5%), including MDR (20.8–29.6%), were observed. Notably, 60% (6/10) of the simultaneous nasal and oral carriers exhibited different antibiotic resistance profiles between cavities. This study demonstrates the relevance of the oral cavity as an independent colonization site for S. aureus and as a potential source of antimicrobial resistance, a role which has been widely neglected so far. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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13 pages, 1024 KiB  
Article
Potential Pathogenic and Opportunistic Oral Bacteria in Early Life: The Role of Maternal Factors in a Portuguese Population
by Mariana Fernandes, Maria João Azevedo, Carla Campos, Ana Filipa Ferreira, Álvaro Azevedo, Inês Falcão-Pires, Egija Zaura, Carla Ramalho, Joana Campos and Benedita Sampaio-Maia
Pathogens 2023, 12(1), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12010080 - 03 Jan 2023
Cited by 1 | Viewed by 2197
Abstract
In early life, maternal factors are of the utmost relevance for oral microbiome acquisition and maturation. Therefore, our study explored the impact of maternal factors, such as saliva and breastmilk colonization, cardiovascular risk factors (CRF), type of delivery, oral health, and caregiving habits [...] Read more.
In early life, maternal factors are of the utmost relevance for oral microbiome acquisition and maturation. Therefore, our study explored the impact of maternal factors, such as saliva and breastmilk colonization, cardiovascular risk factors (CRF), type of delivery, oral health, and caregiving habits on the prevalence of potential pathogenic and opportunistic oral bacteria in early life. A total of 26 healthy mothers, 23 mothers with CRF, and their 50 children were included and samples (child’s oral swabs, mother’s saliva, and breastmilk) were collected 4 to 12 weeks after delivery and inoculated in selective and differential media for detection of non-fastidious Gram-negative and Gram-positive bacteria to isolate potential pathogenic and opportunistic bacteria identified by MALDI-TOF MS (414 isolates). Within mother–child dyads, the same species were identified in 86% of the pairs and potential pathogenic microorganisms from the Staphylococcaceae and Enterobacteriaceae families were found to be statistically significantly concordant between mother–child samples, particularly in the healthy group. Staphylococcus saprophyticus and Stenotrophomonas maltophilia oral colonization in mother–child pairs were associated with the presence of CRF. Breastfeeding was related to the early life oral colonization of Staphylococcus epidermidis in children from healthy mothers and C-section was associated with higher diversity of pathogens, independent of cardiovascular status (p = 0.05). This study reveals the presence of potential oral opportunistic and pathogenic bacteria in early life and highlights the importance of maternal factors in its acquisition. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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13 pages, 496 KiB  
Article
Subgingival Periopathogens Assessment and Clinical Periodontal Evaluation of Gastric Cancer Patients—A Cross Sectional Pilot Study
by Flavia Mirela Nicolae, Andreea Cristiana Didilescu, Petra Șurlin, Bogdan Silviu Ungureanu, Valeriu Marin Șurlin, Ștefan Pătrașcu, Sandu Ramboiu, Igor Jelihovschi, Luminita Smaranda Iancu, Mirela Ghilusi, Mihai Cucu and Dan Ionuț Gheonea
Pathogens 2022, 11(3), 360; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11030360 - 16 Mar 2022
Cited by 3 | Viewed by 2256
Abstract
Oral microbiota have shown a higher bacterial diversity in patients with cancers of the digestive tract, with higher levels of periopathogens. Recent studies have shown that Fusobacterium links to gastro-intestinal neoplastic tissue and accelerates its progression, as well as worsening patient outcome. The [...] Read more.
Oral microbiota have shown a higher bacterial diversity in patients with cancers of the digestive tract, with higher levels of periopathogens. Recent studies have shown that Fusobacterium links to gastro-intestinal neoplastic tissue and accelerates its progression, as well as worsening patient outcome. The present pilot study was carried out between February and December 2020 to evaluate the possible association between the abundance of some periopathogens (Fusobacterium nucleatum, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella forsythia) in subgingival plaque and periodontal status with characteristics of gastric cancer. The study was performed on a sample of 24 patients with gastric cancer from the 1st Department of Surgery and Department of Gastroenterology within the Clinical County Hospital of Emergency of Craiova, Romania. The patients’ oral cavity was examined, gingival crevicular samples were collected, and signs of periodontal disease were recorded. On the histopathological exam, the differentiation grade and size of the tumour were registered. Our results showed that, from the periopathogens studied, the most abundant bacteria were F. nucleatum followed by T. forsythia in all groups. In our present study, the strong correlation between tumour dimension and all periodontal parameters but also between tumour dimension and F. nucleatum could suggest a positive association between periodontal disease, tumoral growth and periopathogens implication in this process. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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13 pages, 2234 KiB  
Article
Odontogenic Cervicofacial Necrotizing Fasciitis: Microbiological Characterization and Management of Four Clinical Cases
by Sebastian Böttger, Silke Zechel-Gran, Daniel Schmermund, Philipp Streckbein, Jan-Falco Wilbrand, Michael Knitschke, Jörn Pons-Kühnemann, Torsten Hain, Markus Weigel, Can Imirzalioglu, Hans-Peter Howaldt, Eugen Domann and Sameh Attia
Pathogens 2022, 11(1), 78; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11010078 - 09 Jan 2022
Cited by 9 | Viewed by 2359
Abstract
Necrotizing fasciitis of the head and neck is a rare, very severe disease, which, in most cases, originates from odontogenic infections and frequently ends with the death of the patient. Rapid surgical intervention in combination with a preferably pathogen-specific antibiotic therapy can ensure [...] Read more.
Necrotizing fasciitis of the head and neck is a rare, very severe disease, which, in most cases, originates from odontogenic infections and frequently ends with the death of the patient. Rapid surgical intervention in combination with a preferably pathogen-specific antibiotic therapy can ensure patients’ survival. The question arises concerning which pathogens are causative for the necrotizing course of odontogenic inflammations. Experimental 16S-rRNA gene analysis with next-generation sequencing and bioinformatics was used to identify the microbiome of patients treated with an odontogenic necrotizing infection and compared to the result of the routine culture. Three of four patients survived the severe infection, and one patient died due to septic multiorgan failure. Microbiome determination revealed findings comparable to typical odontogenic abscesses. A specific pathogen which could be causative for the necrotizing course could not be identified. Early diagnosis and rapid surgical intervention and a preferably pathogen-specific antibiotic therapy, also covering the anaerobic spectrum of odontogenic infections, are the treatments of choice. The 16S-rRNA gene analysis detected significantly more bacteria than conventional methods; therefore, molecular methods should become a part of routine diagnostics in medical microbiology. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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14 pages, 3319 KiB  
Article
Differential Incidence of Tongue Base Cancer in Male and Female HPV16-Transgenic Mice: Role of Female Sex Hormone Receptors
by Clariano Pires de Oliveira Neto, Beatriz Medeiros-Fonseca, Diogo Estêvão, Verónica F. Mestre, Natália R. Costa, Fábio Evangelista de Andrade, Paula A. Oliveira, Margarida M. S. M. Bastos, Rui Medeiros, Diogo Assis, Ana Félix, Fernanda Ferreira Lopes, Rui M. Gil da Costa, Haissa O. Brito and Luciane M. O. Brito
Pathogens 2021, 10(10), 1224; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101224 - 22 Sep 2021
Cited by 3 | Viewed by 2072
Abstract
A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC [...] Read more.
A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ERα) and beta (ERβ), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERβ expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERβ and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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Review

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16 pages, 1241 KiB  
Review
The Roles and Interactions of Porphyromonas gingivalis and Fusobacterium nucleatum in Oral and Gastrointestinal Carcinogenesis: A Narrative Review
by Bing Wang, Juan Deng, Valentina Donati, Nabeel Merali, Adam E. Frampton, Elisa Giovannetti and Dongmei Deng
Pathogens 2024, 13(1), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens13010093 - 20 Jan 2024
Viewed by 1675
Abstract
Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from [...] Read more.
Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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17 pages, 1262 KiB  
Review
Oral Cavity and Candida albicans: Colonisation to the Development of Infection
by Mrudula Patel
Pathogens 2022, 11(3), 335; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11030335 - 10 Mar 2022
Cited by 39 | Viewed by 8857
Abstract
Candida colonisation of the oral cavity increases in immunocompromised individuals which leads to the development of oral candidiasis. In addition, host factors such as xerostomia, smoking, oral prostheses, dental caries, diabetes and cancer treatment accelerate the disease process. Candida albicans is the primary [...] Read more.
Candida colonisation of the oral cavity increases in immunocompromised individuals which leads to the development of oral candidiasis. In addition, host factors such as xerostomia, smoking, oral prostheses, dental caries, diabetes and cancer treatment accelerate the disease process. Candida albicans is the primary causative agent of this infection, owing to its ability to form biofilm and hyphae and to produce hydrolytic enzymes and candialysin. Although mucosal immunity is activated, from the time hyphae-associated toxin is formed by the colonising C. albicans cells, an increased number and virulence of this pathogenic organism collectively leads to infection. Prevention of the development of infection can be achieved by addressing the host physiological factors and habits. For maintenance of oral health, conventional oral hygiene products containing antimicrobial compounds, essential oils and phytochemicals can be considered, these products can maintain the low number of Candida in the oral cavity and reduce their virulence. Vulnerable patients should be educated in order to increase compliance. Full article
(This article belongs to the Special Issue Opportunistic Oral Pathogens in Oral and Systemic Diseases)
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