Oral pathogenesis of Aggregatibacter actinomycetemcomitans

Gholizadeh, Pourya; Pormohammad, Ali; Eslami, Hosein; Shokouhi, Behrooz; Fakhrzadeh, Vahid; Kafil, Hossein Samadi

doi:10.1016/j.micpath.2017.11.001

Cited by 108 publications

(93 citation statements)

References 144 publications

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“…At this point, it is necessary to highlight that the association between IL‐22–expressing CD4 + AhR + T lymphocytes and alveolar bone resorption proposed in the present study is based only on correlation data; thus, additional and rigorous cause‐and‐effect experiments are required, in order to ratify their periodontopathogenic role. In addition, this association was established using an animal model of experimental periodontitis induced with A. actinomycetemcomitans , which has been widely associated with severe forms of the disease in humans; thus, the data presented here should be taken with caution in the context of less periodontopathogenic bacteria and the complexity of the periodontal microbiome.…”

Section: Discussionmentioning

confidence: 98%

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Monasterio

Budini

Fernández

et al. 2019

J of Periodontal Research

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Background and Objective Over the past few years, the importance of interleukin‐22 (IL‐22) and T‐helper (Th)22 lymphocytes in the pathogenesis of periodontitis has become apparent; however, there are still aspects that are not addressed yet. Cells expressing IL‐22 and aryl hydrocarbon receptor (AhR), transcription factor master switch gene implicated in the differentiation and function of Th22 lymphocytes, have been detected in periodontal tissues of periodontitis‐affected patients. In addition, IL‐22 has been associated with osteoclast differentiation and their bone resorptive activity in vitro. However, the destructive potential of IL‐22–expressing AhR+ Th22 lymphocytes over periodontal tissues during periodontitis has not been demonstrated in vivo yet. Therefore, this study aimed to analyze whether IL‐22–expressing CD4+AhR+ T lymphocytes detected in periodontal lesions are associated with alveolar bone resorption during experimental periodontitis. Material and Methods Using a murine model of periodontitis, the expression levels of IL‐22 and AhR, as well as the Th1‐, Th2‐, Th17‐ and T regulatory‐associated cytokines, were analyzed in periodontal lesions using qPCR. The detection of CD4+IL‐22+AhR+ T lymphocytes was analyzed in periodontal lesions and cervical lymph nodes that drain these periodontal lesions using flow cytometry. In addition, the expression of the osteoclastogenic mediator called receptor activator of nuclear factor‐κB ligand (RANKL) was analyzed by qPCR, western blot, and immunohistochemistry. Finally, alveolar bone resorption was analyzed using micro‐computed tomography and scanning electron microscopy, and the bone resorption levels were correlated with IL‐22 and RANKL expression. Results Higher levels of IL‐22, AhR, and RANKL, as well as IL‐1β, IL‐6, IL‐12, IL‐17, IL‐23, and TNF‐α, were expressed in periodontal lesions of infected mice compared with periodontal tissues of sham‐infected and non‐infected controls. Similarly, high RANKL immunoreaction was observed in periodontal tissues of infected mice; however, few or absent RANKL immunoreaction was observed in controls. This association between RANKL and periodontal infection was ratified by western blot. Furthermore, a higher detection of CD4+IL‐22+AhR+ T lymphocytes was found in periodontal lesions and cervical lymph nodes that drain these periodontal lesions in infected mice compared with non‐infected controls. Finally, the increased IL‐22 and RANKL expression showed positive correlation between them and with the augmented alveolar bone resorption observed in experimental periodontal lesions. Conclusion This study demonstrates the increase of IL‐22–expressing CD4+AhR+ T lymphocytes in periodontitis‐affected tissues and shows a positive correlation between IL‐22, RANKL expression, and alveolar bone resorption.

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Section: Discussionmentioning

confidence: 98%

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Monasterio

Budini

Fernández

et al. 2019

J of Periodontal Research

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“…The pathogens containing P5PA are closely associated with respiratory diseases and systemic infections in swine (Actinobacillus (22)), rabbits, hares, ruminants (Actinobacillus(23), Mannheimia (24) and Pasteurella (25,26)), mice (Muribacter (27)) and birds (Pasteurella (25,26) and Gallibacterium (28)). Moreover, P5PA-encoding bacteria in the genus Aggregatibacter are human pathogens and are implicated as the dominant cause of infective endocarditis, brain abscesses (A. aphrophilus) and periodontal diseases (A. actinomycetemcomitans) (29,30). Taken together, most of the pathogens in the bacterial family Pasteurellaceae possess the P5PA vitamin B 6 uptake system.…”

Section: P5pa Are Conserved In Pathogenic Strains Of Pasteurellaceae mentioning

confidence: 99%

Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B₆

Pan

Zimmer

Shah

et al. 2020

Preprint

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416) 946-3048; Running title: Structure and Function of a PLP periplasmic binding protein in Actinobacillus Biological Sciences, Microbiology AbstractBacteria require high efficiency uptake systems to survive and proliferate in nutrient limiting environments, such as those found in the host. The ABC transporters at the bacterial plasma membrane provide a mechanism for transport of many substrates. We recently demonstrated that an AfuABC operon, previously annotated as encoding a ferrous iron uptake system, is in fact a cyclic hexose/heptosephosphate transporter with high selectivity and specificity for these metabolites. In this study, we examine a second operon containing a periplasmic binding protein discovered in Actinobacillus for its potential role in nutrient acquisition. Using electron density obtained from the crystal structure of the periplasmic binding protein we modeled a pyridoxal-5'-phosphate (P5P/PLP/Vitamin B 6 ) ligand into the atomic resolution electron density map. The identity of the Vitamin B 6 bound to this periplasmic binding protein was verified by isothermal titration calorimetry, microscale thermophoresis, and mass spectrometry, leading us to name the protein P5PA and the operon P5PAB. To illustrate the functional utility of this uptake system, we introduced the P5PAB operon from A. pleuropneumoniae into an E. coli K-12 strain that was devoid of a key enzyme required for Vitamin B 6 synthesis. The growth of this strain at low levels of Vitamin B 6 supports the role of this newly identify operon in Vitamin B 6 uptake.

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“…Following periodontal therapy, especially surgical treatment, A. actinomycetemcomitans was less frequently detected in patients with AP than in those with CP [4]. A. actinomycetemcomitans possesses several virulence factors, that is, lipopolysaccharides that induce pro-inflammatory cytokines, a cytolethal distending toxin causing cell cycle arrest in T-cells, macrophages and epithelial cells, and a leukotoxin [5]. The leukotoxin produced by the bacterium is capable of killing or inactivating immune cells and of inducing the release of interleukin (IL)-1β [6].…”

Section: Introductionmentioning

confidence: 99%

JP2 Genotype of Aggregatibacter actinomycetemcomitans in Caucasian Patients: A Presentation of Two Cases

2020

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Aggregatibacter actinomycetemcomitans is a key pathogen that has been associated with periodontal disease. Its most important virulence factor is a leukotoxin capable of inactivating immune cells. The JP2 genotype of Aggregatibacter actinomycetemcomitans shows enhanced leukotoxic activity and is mostly present in individuals of North and West African origin with severe periodontitis. In this paper, two cases of Caucasians diagnosed with the JP2 genotype are presented. A 50-year-old female patient had three approximal sites with ≥ 6 mm clinical attachment loss (CAL) and eight sites with probing depth (PD) ≥ 5 mm. Microbiological diagnostics revealed A. actinomycetemcomitans JP2 genotype, but not Porphyromonas gingivalis. This JP2 genotype was highly leukotoxic to monocytic cells. The second case was a 55-year-old female patient with CAL of > 5 mm at all molars and PD of up to 12 mm. A. actinomycetemcomitans JP2 was identified, but not P. gingivalis. Her husband originated from North-Africa. In him, no A. actinomycetemcomitans was detected, but their 17-year-old daughter was diagnosed with periodontitis and was found to be positive for the JP2 genotype. Both patients were successfully treated with adjunctive antibiotics and the JP2 genotype was eliminated. In summary, here, the microbiological diagnosis was key for the treatment with adjunctive antibiotics.

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Oral pathogenesis of Aggregatibacter actinomycetemcomitans

Cited by 108 publications

References 144 publications

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B₆

JP2 Genotype of Aggregatibacter actinomycetemcomitans in Caucasian Patients: A Presentation of Two Cases

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Oral pathogenesis of Aggregatibacter actinomycetemcomitans

Cited by 108 publications

References 144 publications

IL‐22–expressing CD4+AhR+ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

IL‐22–expressing CD4+AhR+ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B6

JP2 Genotype of Aggregatibacter actinomycetemcomitans in Caucasian Patients: A Presentation of Two Cases

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IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

IL‐22–expressing CD4⁺AhR⁺ T lymphocytes are associated with RANKL‐mediated alveolar bone resorption during experimental periodontitis

Actinobacillusutilizes a binding-protein dependent ABC transporter to acquire Vitamin B₆