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.

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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.

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.

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