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Colloids and Surfaces. B, Biointerfaces Jun 2024Antibiotic resistance has become an urgent threat to health care in recent years. The use of drug delivery systems provides advantages over conventional administration...
Toxin-triggered liposomes for the controlled release of antibiotics to treat infections associated with the gram-negative bacterium, Aggregatibacter actinomycetemcomitans.
Antibiotic resistance has become an urgent threat to health care in recent years. The use of drug delivery systems provides advantages over conventional administration of antibiotics and can slow the development of antibiotic resistance. In the current study, we developed a toxin-triggered liposomal antibiotic delivery system, in which the drug release is enabled by the leukotoxin (LtxA) produced by the Gram-negative pathogen, Aggregatibacter actinomycetemcomitans. LtxA has previously been shown to mediate membrane disruption by promoting a lipid phase change in nonlamellar lipids, such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-methyl (N-methyl-DOPE). In addition, LtxA has been observed to bind strongly and nearly irreversibly to membranes containing large amounts of cholesterol. Here, we designed a liposomal delivery system composed of N-methyl-DOPE and cholesterol to take advantage of these interactions. Specifically, we hypothesized that liposomes composed of N-methyl-DOPE and cholesterol, encapsulating antibiotics, would be sensitive to LtxA, enabling controlled antibiotic release. We observed that liposomes composed of N-methyl-DOPE were sensitive to the presence of low concentrations of LtxA, and cholesterol increased the extent and kinetics of content release. The liposomes were stable under various storage conditions for at least 7 days. Finally, we showed that antibiotic release occurs selectively in the presence of an LtxA-producing strain of A. actinomycetemcomitans but not in the presence of a non-LtxA-expressing strain. Together, these results demonstrate that the designed liposomal vehicle enables toxin-triggered delivery of antibiotics to LtxA-producing strains of A. actinomycetemcomitans.
Topics: Liposomes; Anti-Bacterial Agents; Aggregatibacter actinomycetemcomitans; Delayed-Action Preparations; Drug Liberation; Cholesterol; Microbial Sensitivity Tests; Exotoxins; Phosphatidylethanolamines; Drug Delivery Systems
PubMed: 38555763
DOI: 10.1016/j.colsurfb.2024.113870 -
Nephrology (Carlton, Vic.) Mar 2024Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks...
Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.
PubMed: 38544475
DOI: 10.1111/nep.14298 -
Exploring the In Vitro Antibacterial Potential of Specific Probiotic Strains against Oral Pathogens.Microorganisms Feb 2024The microbiota in the oral cavity has a strict connection to its host. Its imbalance may determine oral diseases and can also have an impact on the systemic health....
The microbiota in the oral cavity has a strict connection to its host. Its imbalance may determine oral diseases and can also have an impact on the systemic health. Probiotic strains may help in the restoration of a balanced condition. For this purpose, we screened the antibacterial and antiadhesive activities of many viable probiotic strains ( PBS066, LCR030, LG050, PBS067, PBS072, LRH020, subsp. BL050, LPC 1101, LPC 1082, and LPC 1114) against two main oral pathogens, and , involved in dental caries and periodontal disease development and progression. Considering both the agar overlay preventive and treatment models, seven probiotics determined greater inhibition zones against the tested pathogens. This behavior was further analyzed by the plate count method and scanning electron microscope imaging. PBS067, LRH020, LPC 1101, LPC 1082, and LPC 1114 prevent the growth and adhesion of oral pathogens in a strain-specific manner ( < 0.0001). These probiotics might be considered as an alternative effective adjuvant to improve oral and systemic well-being for future personalized treatments.
PubMed: 38543492
DOI: 10.3390/microorganisms12030441 -
International Journal of Molecular... Mar 2024This study aimed to evaluate the impact of on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning...
This study aimed to evaluate the impact of on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between the control and test conditions. The biofilm developed with at 72 h had a higher bacterial biomass and a significantly higher cell viability ( < 0.05). After both 48 and 72 h of incubation, in the presence of , there was a significant increase in counts of and and in the cell viability of , , , and . Using a dynamic in vitro multispecies biofilm model, exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.
Topics: Candida albicans; Cell Survival; Dental Implants; Biofilms; Porphyromonas gingivalis
PubMed: 38542256
DOI: 10.3390/ijms25063277 -
Toxins Mar 2024is a Gram-negative bacterium associated with localized aggressive periodontitis as well as some systemic diseases. The strains of most closely associated with disease...
is a Gram-negative bacterium associated with localized aggressive periodontitis as well as some systemic diseases. The strains of most closely associated with disease produce more of a secreted leukotoxin (LtxA) than isolates from healthy carriers, suggesting a key role for this toxin in disease progression. LtxA is released into the bacterial cytosol in a free form as well as in association with the surface of outer membrane vesicles (OMVs). We previously observed that the highly leukotoxic strain JP2 produces two populations of OMVs: a highly abundant population of small (<100 nm) OMVs and a less abundant population of large (>300 nm) OMVs. Here, we have developed a protocol to isolate the OMVs produced during each specific phase of growth and used this to demonstrate that small OMVs are produced throughout growth and lack LtxA, while large OMVs are produced only during the exponential phase and are enriched with LtxA. Our results indicate that surface-associated DNA drives the selective sorting of LtxA into large OMVs. This study provides valuable insights into the observed heterogeneity of vesicles and emphasizes the importance of understanding these variations in the context of bacterial pathogenesis.
Topics: Aggregatibacter actinomycetemcomitans; Toxins, Biological; Cytosol; Biological Transport; Cell Movement
PubMed: 38535804
DOI: 10.3390/toxins16030138 -
Journal of Oral Microbiology 2024Gingivitis, i.e. inflammation of the gums, is often induced by dentalplaque. However, its exact link to the oral microbiota remains unclear.
BACKGROUND
Gingivitis, i.e. inflammation of the gums, is often induced by dentalplaque. However, its exact link to the oral microbiota remains unclear.
METHODS
In a case-control study involving 120 participants, comprising 60 cases and 60 controls (mean age (SD) 36.6 (7.6) years; 50% males), nested within a prospective multicentre cohort study, we examined theoral microbiome composition of gingivitis patients and their controlsusing shotgun metagenomic sequencing of saliva samples. Participants underwent clinical and radiographic oral health examinations, including bleeding on probing (BOP), at six tooth sites. BOP ≥33%was considered 'generalized gingivitis/initial periodontitis'(GG/IP), and BOP <33% as 'healthy and localized gingivitis'(H/LG). Functional potential was inferred using HUMANn3.
RESULTS
GG/IP exhibited an increase in the abundance of , whereas H/LG exhibited an increased abundance of . Nineteen bacterial species and fourmicrobial functional profiles, including L-methionine, glycogen, andinosine-5'-phosphate biosynthesis, were associated with GG/IP. Constructing models with multiple markers resulted in a strong predictive value for GG/IP, with an area under the curve (ROC) of 0.907 (95% CI: 0.848-0.966).
CONCLUSION
We observed distinct differences in the oral microbiome between the GG/IP and H/LG groups, indicating similar yet unique microbial profiles and emphasizing their potential role in progression of periodontal diseases.
PubMed: 38528961
DOI: 10.1080/20002297.2024.2330867 -
The Journal of Contemporary Dental... Feb 2024The study aims is to evaluate the antibacterial effect of vitamin D3 against the , in chronic periodontitis patients.
AIM
The study aims is to evaluate the antibacterial effect of vitamin D3 against the , in chronic periodontitis patients.
MATERIALS AND METHODS
The study comprised 98 participants with chronic periodontitis. All clinical parameters including plaque index (PI), gingival bleeding index (GBI), probing pocket depth (PPD), clinical attachment level (CAL), and a microbiological assay of were assessed at the baseline. All study participants who underwent scaling and root planning were divided into two groups, A and B, each with 49 patients and only group B patients were advised to take vitamin D supplementation of 60,000 IU granules, once daily for 2 months. All the patients of both the groups were recalled at the end of 2nd month and all the clinical and microbiological parameters were reassessed.
RESULTS
After two months, there was a reduction in all the clinical markers in both groups, but the group B patients showed more improvement following non-surgical treatment vitamin D intake. There was also a statistical reduction in and following administration of vitamin D in group B patients compared to group A.
CONCLUSION
These discoveries proposed that vitamin D has a superb antimicrobial impact against red complex periodontal microbes and might be considered a promising compound in the counteraction of periodontal disease.
CLINICAL SIGNIFICANCE
Vitamin D is considered to possess anti-inflammatory and antimicrobial activity, which may help to delay the progression of periodontitis. So, vitamin D3 can be used as a potential supplement that could be employed to stop the advancement of periodontal disease. How to cite this article: Govindharajulu R, Syed NK, Sukumaran B, . Assessment of the Antibacterial Effect of Vitamin D3 against Red Complex Periodontal Pathogens: A Microbiological Assay. J Contemp Dent Pract 2024;25(2):114-117.
Topics: Humans; Chronic Periodontitis; Cholecalciferol; Periodontal Pocket; Porphyromonas gingivalis; Anti-Bacterial Agents; Periodontal Attachment Loss; Aggregatibacter actinomycetemcomitans
PubMed: 38514407
DOI: 10.5005/jp-journals-10024-3642 -
Microbiology Spectrum Apr 2024and are two of the most common bacterial genera in the human oral cavity, encompassing both commensals and pathogens of substantial ecological and medical...
UNLABELLED
and are two of the most common bacterial genera in the human oral cavity, encompassing both commensals and pathogens of substantial ecological and medical significance. In this study, we conducted a metapangenomic analysis of oral and species to uncover genomic diversity, phylogenetic relationships, and habitat specialization within the human oral cavity. Using three metrics-pangenomic gene content, phylogenomics, and average nucleotide identity (ANI)-we first identified distinct species and sub-species groups among these genera. Mapping of metagenomic reads then revealed clear patterns of habitat specialization, such as species predominantly in dental plaque, a distinctive sub-species group on the tongue dorsum, and . sp. HMT-036 predominantly in keratinized gingiva and buccal mucosa. In addition, we found that supragingival plaque samples contained predominantly only one out of the three taxa, , , and . sp. HMT-458, suggesting independent niches or a competitive relationship. Functional analyses revealed the presence of key metabolic genes, such as oxaloacetate decarboxylase, correlated with habitat specialization, suggesting metabolic versatility as a driving force. Additionally, heme synthesis distinguishes . sp. HMT-036 from closely related , suggesting that the availability of micronutrients, particularly iron, was important in the evolutionary ecology of these species. Overall, our study exemplifies the power of metapangenomics to identify factors that may affect ecological interactions within microbial communities, including genomic diversity, habitat specialization, and metabolic versatility.
IMPORTANCE
Understanding the microbial ecology of the mouth is essential for comprehending human physiology. This study employs metapangenomics to reveal that various and species exhibit distinct ecological preferences within the oral cavity of healthy individuals, thereby supporting the site-specialist hypothesis. Additionally, it was observed that the gene pool of different species correlates with their ecological niches. These findings shed light on the significance of key metabolic functions in shaping microbial distribution patterns and interspecies interactions in the oral ecosystem.
Topics: Humans; Aggregatibacter; Phylogeny; Ecosystem; Haemophilus; Mouth
PubMed: 38488280
DOI: 10.1128/spectrum.04017-23 -
International Journal of Rheumatic... Mar 2024Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact cause of the disease is not yet fully understood, both environmental factors and genetics may play a role in its development. Moreover, research suggests microbiota contributes to the onset and progression of RA. People with RA show higher quantities of bacteria such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella copri, Proteus mirabilis, and Lactobacillus salivarius compared to healthy individuals. Conversely, studies propose that Lactobacillus casei, a probiotic bacterium with immunomodulatory properties, has beneficial effects for RA in murine and human models. Therefore, this work reviews the potential role of the gut microbiota in the development of RA and explores the feasibility of using probiotic bacteria as a supplementary treatment for this disease.
Topics: Humans; Mice; Animals; Microbiota; Arthritis, Rheumatoid; Gastrointestinal Microbiome; Inflammation; Probiotics
PubMed: 38487975
DOI: 10.1111/1756-185X.15122 -
Thoracic Cancer Apr 2024The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we...
BACKGROUND
The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population.
METHODS
Genetic summary data related to oral microbiota and BC were collected from genome-wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case-control study were used to verify the validity of these findings.
RESULTS
MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case-control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae.
CONCLUSIONS
Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case-control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.
Topics: Female; Humans; Breast Neoplasms; Case-Control Studies; East Asian People; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mouth
PubMed: 38485288
DOI: 10.1111/1759-7714.15280