Biogenesis of Type V pili

Abstract

Pili or fimbriae, which are filamentous structures present on the surface of bacteria, were purified from a periodontal pathogen, Porphyromonas gingivalis, in 1980s. The protein component of pili (stalk pilin), which is its major component, was named FimA; it has a molecular weight of approximately 41 kDa. Because the molecular weight of the pilin from P. gingivalis is twice that of pilins from other bacterial pili, the P. gingivalis Fim pili were suggested to be formed via a novel mechanism. In earlier studies, we reported that the FimA pilin is secreted on the cell surface as a lipoprotein precursor, and the subsequent N-terminal processing of the FimA precursor by arginine-specific proteases is necessary for Fim pili formation. The crystal structures of FimA and its related proteins were determined recently, which show that Fim pili are formed by a protease-mediated strand-exchange mechanism. The most recent study conducted by us, wherein we performed cryoelectron microscopy of the pilus structure, provided evidence in support of this mechanism. As the P. gingivalis Fim pili are formed through novel transport and assembly mechanisms, such pili are now designated as Type V pili. Surface lipoproteins, including the anchor pilin FimB of Fim pili that are present on the outer membrane, have been detected in certain Gram-negative bacteria. Here, we describe the assembly mechanisms of pili, including those of Type V and other pili, as well as the lipoprotein transport mechanisms. K E Y W O R D S bacterial components, lipoprotein, periodontal pathogen, pili 1 | INTRODUCTION Periodontal disease and dental caries are two leading causes of the loss of teeth worldwide. Periodontal disease is more commonly known to cause the loss of teeth than dental caries in people aged 40 years or above in Japan. 1 With age progression, the proportion of people with severe symptoms of periodontal disease increases as well and this tendency is noted approximately until individuals reach 80 years of age. 2,3 Chronic periodontitis is known to be caused by multiple bacteria that inhabit the periodontal pocket and the consequent immune responses. 4 Large-scale epidemiological studies have revealed the bacteria involved in the prevalence of periodontal disease. 5-7 Among periodontopathic bacteria, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola are strongly associated with the onset and progression of chronic periodontitis and are

Towards defining the outer membrane proteome of Porphyromonas gingivalis

“…The presence of the lipoprotein signal suggests that the string of POTRA domains curl back around to the OM (Figure 1). The same P. gingivalis Bam and Tam proteins were also recently predicted by others (Shoji et al., 2020).…”

“…A new type of pilus was recently characterized in P. gingivalis and related species. The type V pilins are produced as lipoproteins and polymerized on the cell surface through proteolytic cleavage of the lipidated N‐terminal region and donor‐strand exchange (Shibata et al., 2020; Shoji et al., 2020; Xu et al., 2016). Three pili have been identified, the major (longer) pili (or fimbriae) composed of Fim subunits, the minor pili composed of Mfa subunits and PG1881 (Nagano et al., 2017), which is yet to be fully characterized (Table ).…”

Diversity analysis of genes encoding Mfa1 fimbrial components in Porphyromonas gingivalis strains

“…The FimA and Mfa1 proteins polymerize to form a filamentous structure by a similar mechanism [22]; via proteolytic processing by a signal peptidase and gingipain to yield the mature forms. Then, the C-terminal donor strands of the incoming monomer extend and bind to the hydrophobic groove of the prior monomer [23,24].…”

“…Then, the C-terminal donor strands of the incoming monomer extend and bind to the hydrophobic groove of the prior monomer [23,24]. This is known as the donor-strand exchange mechanism in the assembly of Escherichia coli fimbriae [25], but unlike in P. gingivalis, chaperone and usher proteins are absent, whereas digestion with protease (gingipain) is involved in maturation [22]. This proteinase-mediated donor-strand exchange mechanism, currently seen only in the class Bacteroidia, is called type V fimbriae [23].…”

Porphyromonas gingivalis FimA and Mfa1 fimbriae: Current insights on localization, function, biogenesis, and genotype

“…Therefore, P. gingivalis possesses a unique class of fimbria subunits [ [9] , [10] , [11] ]. Recent structural analyses and mechanistic studies of the fimbrial proteins of P. gingivalis [ [23] , [24] , [25] ] indicated that P. gingivalis fimbriae were formed by a proteinase-mediated donor-strand exchange mechanism, which were classified as a novel type of fimbriae and designated as Type V fimbriae [ 23 , [26] , [27] , [28] ]. Structurally homologous fimbrial proteins are detected only in the Bacteroidia class [ 23 ], which are integral parts of the human microbiome and are associated with human health and disease.…”