Bacterial pathogens do not only succeed in breaking the barriers that protect humans from infection, but they also manage to evade insults from the human immune system. The importance of the present study resides in the fact that protein citrullination is shown to represent a new bacterial mechanism for immune evasion. In particular, the oral pathogen P. gingivalis employs this mechanism to defuse innate immune responses by secreting a protein-citrullinating enzyme. Of note, this finding impacts not only the global health problem of periodontitis, but it also extends to the prevalent autoimmune disease rheumatoid arthritis, which has been strongly associated with periodontitis, PPAD activity, and loss of tolerance against citrullinated proteins, such as the histone H3.

in recent decades, chikungunya virus (cHiKV) has re-emerged, leading to outbreaks of chikungunya fever in Africa, Asia and central and South America. the disease is characterized by a rapid onset febrile illness with (poly)arthralgia, myalgia, rashes, headaches and nausea. In 30 to 40% of the cases, CHIKV infection causes persistent (poly)arthralgia, lasting for months or even years after initial infection. Despite the drastic re-emergence and clinical impact there is no vaccine nor antiviral compound available to prevent or control cHiKV infection. Here, we evaluated the antiviral potential of tomatidine towards cHiKV infection. We demonstrate that tomatidine potently inhibits virus particle production of multiple CHIKV strains. Time-of-addition experiments in Huh7 cells revealed that tomatidine acts at a post-entry step of the virus replication cycle. furthermore, a marked decrease in the number of cHiKV-infected cells was seen, suggesting that tomatidine predominantly acts early in infection yet after virus attachment and cell entry. Antiviral activity was still detected at 24 hours post-infection, indicating that tomatidine controls multiple rounds of cHiKV replication. Solasodine and sarsasapogenin, two structural derivatives of tomatidine, also showed strong albeit less potent antiviral activity towards cHiKV. in conclusion, this study identifies tomatidine as a novel compound to combat CHIKV infection in vitro.

Severe periodontitis is a dysbiotic inflammatory disease that affects about 15% of the adult population, making it one of the most prevalent diseases worldwide. Importantly, periodontitis has been associated with the development of nonoral diseases, such as rheumatoid arthritis, pancreatic cancer, and Alzheimer’s disease.