Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases.

Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer's disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.

Inhibition of Porphyromonas gingivalis peptidyl arginine deiminase, a virulence factor, by antioxidant-rich Cratoxylum cochinchinense: In vitro and in silico evaluation.

Porphyromonas gingivalis, the cause of periodontitis, is also linked to many systemic disorders due to its citrullination capability from a unique peptidyl arginine deiminase (PPAD). Protein citrullination is able to trigger an autoimmune response, increasing the severity of rheumatoid arthritis. The main objective of this study is to evaluate the inhibitory activity of Cratoxylym cochinchinense leaves extract towards the PPAD in vitro and in silico. Methanolic extract of Cratoxylum cochinchinense (CCM) was tested for total phenolic and flavonoid contents along with antioxidative assays. Inhibition of PPAD activities was conducted thereafter using recombinant PPAD in cell lysate. Phytocompounds postulated present in the CCM such as mangiferin, vismiaquinone A, δ-tocotrienol and α-tocotrienol and canophyllol were used as ligands in a simulated docking study against PPAD. Results obtained indicated high antioxidant potential in CCM while recording abundant phenolic (129.0 ± 2.5495 mg GA/g crude extract) and flavonoid (159.0 ± 2.1529 mg QE/g crude extract) contents. A dose-dependent inhibition of PPAD was observed when CCM was evaluated at various concentrations. CCM at 1 mg/mL exhibited citrulline concentration of 24.37 ± 3.25 mM which was 5 times lower than the negative control (114.23 ± 3.31 mM). Molecular docking simulation revealed that mangiferin and vismiaquinone A engaged in H-bonding and pi-pi interactions with important active site residues (Asp130, Arg152, Arg154 and Trp127) of PPAD and could be the potential phytochemicals that accounted for the inhibitory activities observed in the methanolic leaves extract. As such, CCM could be further explored for its therapeutic properties not only for periodontitis, but also for other systemic diseases like rheumatoid arthritis.

Aggregatibacter actinomycetemcomitans as the Aetiological Cause of Rheumatoid Arthritis: What Are the Unsolved Puzzles?

Leukotoxin A (LtxA) is the major virulence factor of an oral bacterium known as Aggregatibacter actinomycetemcomitans (Aa). LtxA is associated with elevated levels of anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) patients. LtxA targets leukocytes and triggers an influx of extracellular calcium into cytosol. The current proposed model of LtxA-mediated hypercitrullination involves the dysregulated activation of peptidylarginine deiminase (PAD) enzymes to citrullinate proteins, the release of hypercitrullinated proteins through cell death, and the production of autoantigens recognized by ACPA. Although model-based evidence is yet to be established, its interaction with the host's immune system sparked interest in the role of LtxA in RA. The first part of this review summarizes the current knowledge of Aa and LtxA. The next part highlights the findings of previous studies on the association of Aa or LtxA with RA aetiology. Finally, we discuss the unresolved aspects of the proposed link between LtxA of Aa and RA.

Antioxidant-rich Clove Extract, A Strong Antimicrobial Agent against Urinary Tract Infections-causing Bacteria in vitro.

Clove (Syzygium aromaticum) is an exotic culinary spice that has been used for centuries due to its known antimicrobial and antioxidant properties. The main aim of this study is to compare the antimicrobial activity and antioxidant capacity of clove ethanolic extract (CEE) and commercial clove essential oil (CEO) at a standardised eugenol content. Disk diffusion assay showed that CEE (2000 µg) was able to exhibit broad-spectrum inhibition against both Gram negative and Gram positive Urinary Tract Infections (UTIs)-causing pathogens: Proteus mirabilis (19.7 ± 0.6 mm) > Staphylococcus epidermidis (18 mm) > Staphylococcus aureus (14.7 ± 0.6 mm) > Escherichia coli (12.7 ± 0.6 mm) > Klebsiella pneumoniae (12.3 ± 0.6 mm) (according to the size of inhibition zone). Interestingly, the comparison between CEE and commercial CEO revealed that the former demonstrated stronger antimicrobial and antioxidative properties at similar eugenol concentration. The EC50 of DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and reducing power assay for CEE were determined as 0.037 mg/mL, 0.68 mg/mL and 0.44 mg/mL, respectively. Besides eugenol, High Performance Liquid Chromatography (HPLC) analyses identified the presence of kaempferol, gallic acid and catechin in CEE. As a conclusion, we concluded that there was a possible synergistic effect between eugenol and the others active compounds especially kaempferol which led to the observed bioactivities in CEE.

Bunga cengkih (Syzygium aromaticum) merupakan salah satu rempah masakan eksotik yang telah digunakan berabad-abad untuk kegunaan antimikrob dan antioksidan. Matlamat utama kajian ini adalah untuk membandingkan aktiviti antimikrob dan kapasiti antioksidan di antara ekstrak etanol bunga cengkih (CEE) dan minyak pati bunga cengkih komersial (CEO) dengan kandungan eugenol yang sama. Pencerakinan resapan agar menunjukkan CEE mempunyai perencatan spektrum yang luas terhadap bakteria Gram negatif dan Gram positif, patogen penyebab jangkitan saluran kencing: Proteus mirabilis (19.7 ± 0.6 mm) > Staphylococcus epidermidis (18 mm) > Staphylococcus aureus (14.7 ± 0.6 mm) > Escherichia coli (12.7 ± 0.6 mm) > Klebsiella pneumoniae (12.3 ± 0.6 mm) (menurut saiz zon perencatan). Yang menarik, perbandingan CEE dan CEO mendedahkan bahawa CEE menunjukkan aktiviti antibakteria yang kuat. Hapus-sisa radikal bebas DPPH dan ABTS serta aktiviti kuasa redaksi untuk rempah ini telah dibandingkan dengan CEO. Keputusan menunjukkan aktiviti antioksidan dalam CEE adalah lebih kuat. EC50 DPPH, ABTS dan pencerakinan kuasa redaksi untuk CEE masing-masing telah ditentukan sebagai 0.037 mg/mL, 0.68 mg/mL and 0.44 mg/mL. Kompaun aktif (eugenol dan lainlain kompaun fenolik) merupakan kompaun yang terkandung dalam CEE. Analisis HPLC mengkuantitikan kehadiran kaempferol, asid galik dan katechin. Kesimpulannya, kita menjangkakan kemungkinan terdapat kesan sinergi di antara eugenol dengan kompaun fenolik lain terutamanya kaempferol yang berupaya meningkatkan aktiviti CEE berbanding dengan CEO.

Draft Genome Sequence of Lactarius deliciosus Strain CBS 582.63 from the CBS-KNAW Culture Collection.

A type strain of Lactarius deliciosus was obtained from the CBS-KNAW culture collection. The mycelium was cultured using potato dextrose agar, and the extracted genomic DNA was subjected to PacBio genome sequencing. Upon assembly and annotation, the genome size was estimated to be 54 Mbp, with 12,753 genes.

Genome Sequence of a Gram-Positive Diazotroph, Paenibacillus durus Type Strain ATCC 35681.

Here, we report the complete genome sequence of Paenibacillus durus type strain ATCC 35681, which can fix atmospheric nitrogen even in the presence of nitrate.