These proteins are predicted to reside in the IM, which would be consistent with the localization of the LolCE proteins of phylum (63)

These proteins are predicted to reside in the IM, which would be consistent with the localization of the LolCE proteins of phylum (63). appearance is more reminiscent of a little sausage (Fig. 1). initially garnered interest as a model organism for bacteria of the (CFB) group and, later on, as an oral pathogen. The focus on has recently peaked with the discovery of a new protein secretion system (1) and with the evidence of its involvement in Alzheimers disease (2). However, this bacterium is best known as a major etiological agent N3PT of the oral disease periodontitis (3, 4), being present in almost 85% of severe cases (5,C7). Periodontitis is an inflammatory disorder affecting the tissue surrounding the teeth, the periodontium, potentially leading to tooth loss. Severe forms of periodontitis have a global prevalence of 11%. However, depending on the degree of severity, socioeconomic status, and oral hygiene, this disease can affect up to 57% of particular N3PT populations (8, 9). In the United States, for example, 46% N3PT of adults are affected by this disorder, with 8.9% presenting severe forms (9). This extremely high incidence establishes periodontitis as one of the most common diseases and as the main cause of tooth loss worldwide (9, 10). Open in a separate window FIG 1 type strain W83 (A) and the clinical strains 505700 (B), 512915 (C), 505759 (D), and MDS33 (E and F). Note the capture of OMV formation in panels A, B, C, and E (marked by white arrows). Interestingly, periodontitis has been associated with several health conditions, such as diabetes, heart diseases, Alzheimers disease, and rheumatoid arthritis (RA). In the case of diabetes, a two-way relationship was proposed, where the inflammatory mediators released in response to a periodontal infection would have an adverse effect on glycemic control, while diabetes-driven N3PT factors such as impaired chemotaxis, reduced collagen synthesis, and increased collagenase production would, in turn, enhance the Rabbit polyclonal to AMHR2 severity of periodontitis (11,C16). The association between periodontitis and heart diseases, on the other hand, is more tenuous than the one with diabetes, and no potential mechanistic links are currently known (17,C19). Investigations on the association of periodontitis with dementia support the potential involvement of periodontitis in this cognitive disorder both at the immunomodulatory level, which would relate to the systemic inflammatory responses caused by this oral disease, and at the physiological level, which could relate to possible micronutrient deficiencies (e.g., for thiamine and vitamin B12) that may arise from dietary changes as a consequence of tooth loss and that potentially lead to cognitive impairment (20, 21). A special case has been made for the most common type of dementia, Alzheimers disease, where has been proposed to play a significant role (2, 20,C23). In particular, it was suggested that the secretion of particular cysteine proteases called gingipains may cause neuronal damage, which would be supported by the N3PT fact that these proteases, along with bacterial DNA, were detected in the brains of Alzheimers disease patients (2). Lastly, the association of periodontitis with RA has been studied most intensively (24,C42). RA is an inflammatory autoimmune disorder for which the etiology is still not fully understood and that is clinically associated with periodontitis. In several countries, the prevalence of periodontitis was reported to be increased among RA patients in comparison with the general population (24, 29, 36, 37, 40, 43, 44). Correspondingly, RA was found to be more prevalent among patients with periodontitis (35,C37, 40, 44), which supports the hypothesis that an intimate connection exists between the two disorders. The suspected role of in the interplay between periodontitis and RA has drawn attention to the bacteriums citrullinating enzyme (25, 27, 28, 32, 34, 41). This enzyme, a peptidylarginine deiminase (PAD), catalyzes the conversion of arginine into citrulline residues in a posttranslational protein modification called citrullination. Citrullination can alter the net charge of a substrate protein, possibly leading to severe changes in its structure and function (27). Although citrullination is a physiological process that takes place in a wide variety of healthy tissues as a general regulatory mechanism, especially during apoptosis, it is also associated with inflammatory processes. Although peptidylarginine deiminases are highly conserved in mammals, only three bacteria of the genus are known to produce such enzymes (27, 38, 45,C47). The PAD of (PPAD) and the homologous enzymes from and share no evolutionary relationship with the mammalian PADs (47, 48). Remarkably, PPAD is believed to citrullinate certain human host.