Abstract
Porphyromonas gingivalis, a pathogen of chronic periodontitis, is an asaccharolytic microorganism that solely utilizes nutritional amino acids as its energy source and cellular constituents. The bacterium is considered to incorporate proteinaceous nutrients mainly as dipeptides, thus exopeptidases that produce dipeptides from polypeptides are critical for survival and proliferation. We present here an overview of dipeptide production by P. gingivalis mediated by dipeptidyl‐peptidases (DPPs), e.g., DPP4, DPP5, DPP7, and DPP11, serine exopeptidases localized in periplasm, which release dipeptides from the N‐terminus of polypeptides. Additionally, two other exopeptidases, acylpeptidyl‐oligopeptidase (AOP) and prolyl tripeptidyl‐peptidase A (PTP‐A), which liberate N‐terminal acylated di‐/tri‐peptides and tripeptides with Pro at the third position, respectively, provide polypeptides in an acceptable form for DPPs. Hence, a large fraction of dipeptides is produced from nutritional polypeptides by DPPs with differential specificities in combination with AOP and PTP‐A. The resultant dipeptides are then incorporated across the inner membrane mainly via a proton‐dependent oligopeptide transporter (POT), a member of the major facilitator superfamily. Recent studies also indicate that DPP4 and DPP7 directly link between periodontal and systemic diseases, such as type 2 diabetes mellitus and coagulation abnormality, respectively. Therefore, these dipeptide‐producing and incorporation molecules are considered to be potent targets for prevention and treatment of periodontal and related systemic diseases.
Highlights
Periodontal disease, a bacterial-associated inflammatory condition that occurs around the gingivae, is a leading cause of tooth loss in adults, with 20%–50% of individuals affected worldwide, which results in a decrement in overall quality of life especially in elderly individuals (Nazir, 2017)
A large number of epidemiological studies have shown a keen association of chronic periodontitis and type 2 diabetes mellitus (Grossi & Genco, 1998; Lalla & Papapanou, 2011; Preshaw et al, 2012), and recently much attention has been given to this oral disease because of its close relationship to systemic diseases, such as atherosclerotic cardiovascular disorder (Genco & VanDyke, 2010; Tabeta et al, 2014), decreased kidney function (Kshirsagar et al, 2007), rheumatoid arthritis (Detert et al, 2010), and Alzheimer's disease (Dominy et al, 2019; Teixeira et al, 2017)
Since nutritional polypeptides are mainly incorporated as dipeptides in bacterial cells, they should be initially degraded into oligopeptides by endopeptidases, and Lys- and Arg-gingipains located at the outer membrane, and degraded into dipeptides by DPP4, DPP5, DPP7, and DPP11
Summary
Periodontal disease, a bacterial-associated inflammatory condition that occurs around the gingivae, is a leading cause of tooth loss in adults, with 20%–50% of individuals affected worldwide, which results in a decrement in overall quality of life especially in elderly individuals (Nazir, 2017). DPPs are exopeptidases that liberate dipeptides from the unblocked N-terminus of oligopeptides and proteins, with eight members classified by amino acid sequence similarity and substrate specificities; DPP1–6 (or I–VI), 7, and 11.
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