Oral Pathogens
The human oral cavity hosts one of the most diverse microbiomes, second only to the gut, with over 700 microbial species forming intricate biofilms. Research in the Zeytuni lab focuses on understanding the complexities of these microbial communities, particularly the role of Porphyromonas gingivalis—a key pathogen in periodontitis. This chronic inflammatory disease, characterized by the destruction of periodontal tissue and bone, affects a significant portion of the population and has been linked to systemic conditions such as cardiovascular disease, rheumatoid arthritis, and Alzheimer's disease.
The Zeytuni laboratory seeks to unravel the mechanisms by which P. gingivalis thrives within dysbiotic biofilms, conferring resistance to host defenses and antibiotics. With the rise of antibiotic resistance and the limitations of current treatments, our goal is to develop novel therapeutic strategies to combat these resilient infections and improve both oral and systemic health. Through innovative research, we aim to contribute to the future of periodontal disease treatment and prevention.
Our multidisciplinary approach combines cutting-edge structural biology techniques, including cryo-electron microscopy, cryo-electron tomography, and X-ray crystallography, complemented by a wide array of in vitro biochemical and biophysical methods, as well as microbiological and cell biology approaches in vivo.
Why Oral Health Matters?
Oral health is a vital component of overall well-being, influencing not just dental health but systemic health throughout the body. Our research sheds light on the connection between oral pathogens, particularly P. gingivalis, and their broader impact on health. By studying how these bacteria contribute to periodontal disease and their links to conditions such as cardiovascular disease, diabetes, and Alzheimer's disease, we aim to contribute to the development of innovative treatments that address not only oral infections but also their systemic effects.
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Prevention of Systemic Diseases - Poor oral health, particularly infections like periodontitis, has been strongly linked to systemic health problems such as cardiovascular disease, diabetes, and Alzheimer's disease. Oral bacteria can enter the bloodstream, causing inflammation and increasing the risk of these conditions.
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Infection Control - Proper oral hygiene helps prevent infections like abscesses and gum disease, which, if left untreated, can spread to other parts of the body and lead to serious complications.
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Improved Pregnancy Outcomes - Research shows that poor oral health in pregnant women, especially periodontitis, is associated with adverse outcomes like premature birth and low birth weight. Good oral care during pregnancy is essential for better health outcomes for both mother and baby.
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Reduction of Chronic Inflammation - Periodontal disease triggers chronic inflammation, which can have far-reaching effects on the body. It is linked to a range of health issues, including heart disease, arthritis, cancer, and even Alzheimer's disease.
Maintaining oral health is not just about a healthy smile—it is key to preventing chronic conditions and ensuring overall well-being.
What Do We Study?
Virulence Factors
Virulence factors are essential for P. gingivalis to establish infections, degrade host tissues, and evade immune responses. These factors contribute to the progression of periodontal disease and are the focus of much of our research.
The Zeytuni lab explores how these virulence factors function and interact with host tissues, providing critical insights into the pathogenic strategies of P. gingivalis. By targeting these factors, we aim to contribute to the development of more effective treatments to combat periodontal disease and the systemic effects of chronic infections.
Virulence Factors Regulation via Two-Component Systems
A key area of our research is understanding how P. gingivalis regulates its virulence factors. We focus on two-component systems (TCS), which are essential for the bacterium’s ability to sense and adapt to changes in its environment. TCS control the expression of key virulence factors, such as proteases, adhesins, and toxins, allowing P. gingivalis to evade immune responses and establish infections.
By studying these regulatory pathways, we aim to uncover new therapeutic targets within the two-component systems. Disrupting these regulatory networks could weaken the bacterium's ability to defend itself and survive, offering a novel strategy to combat infections. Our goal is to translate these findings into new treatments that are more effective against antibiotic-resistant strains of P. gingivalis.
Virulence Factor Secretion: The Type IX Secretion System (T9SS)
The Type IX Secretion System (T9SS) is a critical component of P. gingivalis' ability to facilitate disease. This specialized machinery is responsible for the secretion of essential virulence factors, such as proteases and adhesins, that degrade host tissues and promote infection. Our research focuses on understanding the molecular mechanisms of the T9SS, including the components that facilitate the precise transport of virulence factors from within the bacterium to its surface or into the host environment.
By investigating the T9SS, we aim to identify new ways to disrupt the secretion of pathogenic proteins, potentially rendering P. gingivalis and other oral pathogens unable to cause damage to host tissues. Targeting the T9SS could provide a promising therapeutic strategy for treating periodontal disease and preventing the chronic inflammation and systemic health issues associated with P. gingivalis infections.