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Elucidation of Biogenesis Mechanism and Structure of Fimbria From Impact Objectives • Characterise the structure of Mfa1 fimbria from Porphyromonas gingivalis • Identify the binding partner of the tip protein of Mfa1 fimbria • Devise a new therapeutic strategy for the inhibition of colonisation of this organism The truth about plaque Dr Yoshiaki Hasegawa has thoroughly investigated the mechanisms behind bacteria contributing to periodontal disease. He elaborates on his work and explains the ultimate therapeutic goal driving his research You have a research (including P. gingivalis), also, the fimbria of bacterial flora inhabiting the intestinal tract. background in this family is a new fimbriae which does not microbiology. What belong to any type of bacterial fimbriae (type How do you envisage your research will interests you about I to IV), therefore they named it as V-type be translated into improved dental care this field? fimbriae. I believe that the discovery of these outcomes? new V-type fimbriae has a major impact on Periodontal disease microbiology research. I am very pleased In the future, we hope to lead in the is the most prevalent infectious disease in that the results of our research over the last development of treatment of locally the world and it has been shown that it is 10 years have led to the discovery of new administering substances or peptides associated with various systemic diseases. V-type fimbriae. that inhibit biogenesis of fimbria and/or Periodontitis is a chronic inflammatory binding of tip proteins of P. gingivalis after lesion caused by dental plaque, i.e. biofilm, What is the impact of this research? Who a professional plaque removal procedure, but there are still so many vague points will ultimately benefit from this work? such as scaling by a dentist. Actually, about its etiology. In recent years, due to recent research revealed that the addition microbiome analysis and animal model Generally, in cases of fimbriae in many of a portion of peptide of Mfa1 inhibits of periodontal disease, the hypothesis pathogenic bacteria, since the protein polymerisation of Mfa1 protein and biofilm that Porphyromonas gingivalis is a keystone located at the tip of the fimbria often formation of P. gingivalis, as reported by pathogen in causing Dysbiosis of the dental functions as an actual adhesin, it is thought Alaei SR et al. in 2019. plaque bacterial flora has been proposed that the tip protein of Mfa1 fimbria plays and it attracted so much attention. an important adhesin in the colonisation What are you hoping to focus on in the of periodontal tissue. If we can identify the coming year? Since 2007, we began to analyse the binding partner of the tip proteins of Mfa1 structure and function of Mfa1 fimbriae, fimbria, we will be able to elucidate the I am keen to explore how the fimbrilins of also referred to as Mfa1 pili, which is colonisation mechanism of this bacterium; P. gingivalis V-type fimbriae are transported unique to P. gingivalis and which does not furthermore, we can devise a new and arrayed outside of the bacteria. show homology with other fimbrilins, I therapeutic strategy for the inhibition of this There are many unclear points left in its have clarified a part of fimbria structure bacterial colonisation. biogenesis mechanism. I’d like to clarify the and biogenesis mechanism over the past whole picture of V-type fimbriae biogenesis 10 years. In recent years, by a different Since it has been clarified that Bacteroides mechanism. In addition, I would like to take research group, Xu et al., clarified the crystal that forms intestinal bacterial flora has also advantage of this research experience in structure and polymerisation mechanism a V-type fimbriae like P. gingivalis, we hope P. gingivalis to conduct research that will of a group of proteins which predominantly that by developing this research, we will realise the control of resident bacterial flora exists in human microbiomes and is be able to lead the development of a new of the oral cavity and intestinal tract by presumed to be a fimbrilin of Bacterioidia treatment strategy that controls the resident connecting to the fimbriae of Bacteroidia. www.impact.pub 59 Banishing periodontal disease Understanding the complex microbiological systems contributing to infection could greatly improve our treatment options when it comes to gum disease. Dr Yoshiaki Hasegawa is exploring bacteria to do just that in order to improve therapies Periodontal or gum disease, an inflammatory and gums. The earliest stage of the disease Throughout his work, Hasegawa focuses disease caused by infection of the gums is known as gingivitis, which impacts only the on the specific mechanism that allows for and resulting in the collapse of structures gums. But as the disease progresses all of the bacteria to bond with their surroundings. supporting our teeth, is common worldwide, teeth structures, including the ligaments and ‘Fimbriae are hair-like, fibrous feelers that affecting as much as 50 per cent of the bones, are affected. protrude from the surfaces of bacteria and population. If left untreated, there can be are important for adhesion and consequently severe consequences for the soft tissue Past research has theorised that the main bacterial infection,’ he says. Though they are and bone shaping our oral cavities. These culprit in disease advancement is a certain tiny, they have the ability to critically impact kinds of symptoms are seriously distressing grouping of bacteria named the ‘Red on our dental health. for patients seeking merely to chew their complex’. Hasegawa explains that while it is food and perform everyday tasks. With the true that patients with periodontal disease STRUCTURAL COMPLEXITY overwhelming prominence of this condition, harbour these ‘Red complex’ bacteria in their ‘Fimbria (fibrillar structure formed by further research is needed to provide patients dental plaque, many healthy patients also polymerisation of fimbrilins) plays an the comfort they require. possess them. Therefore, presence of the important role in the establishment of ‘Red complex’ cannot be the singular, simple bacteria in the host,’ explains Hasegawa. Fortunately, Dr Yoshiaki Hasegawa at answer in explaining the origins of gum P. gingivalis has two different types of Aichi Gakuin University’s Department of disease. fimbriae, FimA and Mfa1. FimA has been Microbiology is tackling periodontal disease purified and subsequently well documented at its source and paving the way for new However, one group of the ‘Red complex’ and analysed in countries all over the globe. treatments in the future. Through his intense bacteria stands out from the others. P. The study of Mfa1 fimbriae does not advance case study of the bacteria, Hasegawa reveals gingivalis has gained a great amount of FimA fimbriae, but it is demonstrated some of the critical mechanisms allowing attention in some of the most recent that Mfa1 fimbriae play important role for gum disease to flourish and hypothesises periodontology research. ‘It has even been development of biofilm formation and new methods to inhibit its development. called the ‘Keystone pathogen’ as it is co-aggregation to Streptococcus gordonii, thought to play a crucial role in triggering one of the commensal bacteria in the oral UNCOVERING THE ORIGIN biofilm dental plaque bacteria to evolve into cavity. ‘However, the Mfa1 fimbriae have not Many adults around the world suffer from a pathological state,’ Hasegawa outlines. It received the same attention and detailed some form of periodontal disease. It is a supposedly does this by interfering with the information regarding its form, biogenesis disease that occurs to the teeth structure and immune system. In his research Hasegawa mechanisms and relationship to the onset develops as an infection caused by biofilm, further elucidates just how P. gingivalis drives of periodontal disease have not been so or thin coatings of bacteria lining our teeth such detrimental pathology. carefully examined,’ he continues. 60 www.impact.pub Our research will lead to the development of new therapeutic strategies that will specifically inhibit the establishment of this bacterium and control the resident bacterial flora Thus far, Hasegawa and his team have antibiotics commonly does not involve determined that the Mfa1 fimbria is generated targeting specific bacteria. By wiping out all Project Insights via an mfa gene cluster comprised of five types of bacteria, as antibiotics frequently do, proteins: Mfa1, Mfa2, Mfa3, Mfa4 and Mfa5. patients run the risk of not only generating FUNDING ‘The main shaft portion consists of Mfa1 stronger, resistant bacteria as it is impossible • JSPS KAKENHI Grant Numbers while the base which accounts for length to completely eliminate all traces of bacteria, 20890248, 22791783, 25861752 and consists of Mfa2,’ confirms Hasegawa. ‘The but also risk destroying positive bacteria that 16K11466 tip of the fimbria is then formed by a complex could possibly work with our bodies against • Research grant from the Center for Advanced Oral Science, Aichi Gakuin of Mfa3 through Mfa5.’ In further analysing periodontal disease. University the crystal structure of the fimbrilins, his team have proposed a new biogenesis Instead of relying on antibiotics in treating COLLABORATORS mechanism of Mfa1 fimbriae. gum disease, Hasegawa suggests we • Dr Richard J Lamont, Center for shift gears and promote treatment using Functional Microbiomics, Inflammation ‘We hope that the results of these research probiotics, thus improving the quality and Pathogenicity, School of Dentistry, projects will lead to the development of of our oral microbiomes. As mentioned University of Louisville, USA • Dr Karina Persson, Department of new therapeutic and preventive drugs for earlier, Streptococci might have the ability to Chemistry, Umeå University, Sweden periodontal disease that targets P. gingivalis keep the balance of inflammation. Several • Dr Akio Mitani, Department of fimbria,’ Hasegawa states. investigators have also suggested the use Periodontology, School of Dentistry, Aichi of oral symbiotic bacteria Lactobacillus Gakuin University, Japan The significance of his work to microbiology as probiotics for oral health purposes.
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