HEИндивидуална стипендия2023–2025

BIFCOLC-QS · Quorum sensing as a tool to detect and target pro-oncogenic microbial biofilms associated with right-sided colorectal cancer

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-06-15 → 2025-06-14
Финансиране от ЕС: 173 847 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Бактериалната комуникация (quorum sensing) се изучава, за да се разбере как се образуват вредни биофилми при рак на десния дебело срубенок. Разбирането на този процес помага за разработването на пробиотици, които да откриват и атакуват тези бактериални структури.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Quorum sensing as a tool to detect and target pro-oncogenic microbial biofilms associated with right-sided colorectal cancer

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, responsible for approximately 0.90 million deaths in 2022. CRC can be categorized into two major types based on the anatomical location of the tumors. The proximal (right-sided) and distal (left-sided) colons possess anatomical, developmental, and physiological distinctions, including differences in embryonic origin, vascularization, neuronal supply, and microbial composition. These fundamental differences influence disease onset, progression, pathological features, and clinical outcomes. Right-sided CRC is consistently associated with poorer prognosis, greater resistance to treatment, lower survival rates, and a higher risk of recurrence compared to left-sided CRC. Being a multifactorial disease, CRC is also linked to gut microbiome dysbiosis and is closely associated with pro-oncogenic bacterial strains, including Fusobacterium nucleatum, pks+ Escherichia coli, and enterotoxigenic Bacteroides fragilis. These bacteria contribute to tumorigenesis by producing toxins that damage epithelial integrity, promote inflammation, and induce DNA mutations. They often form invasive polymicrobial biofilms that enhance tumor progression, particularly in right-sided CRC, where such biofilms are more prevalent. Biofilm development is regulated by quorum sensing (QS), a bacterial communication system in which small signaling molecules coordinate the expression of virulence genes and interactions between species The current project has focused on elucidating the role of QS in regulating polymicrobial biofilm formation by CRC-associated bacteria and on developing a probiotic strain capable of sensing these QS signals to identify and target pro-oncogenic biofilms. This approach is being explored as a potential alternative to antibiotics and natural probiotics, which show limited efficacy against biofilms. Targeting CRC-associated microbial biofilms may help limit biofilm-associated disease progression in CRC and reduce disease severity. Furthermore, if administered in the early stages of CRC, it could slow disease progression and prevent recurrence following treatment.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Colorectal cancer (CRC) development and progression have been linked to the presence of pro-oncogenic bacterial strains in the intestine, such as Fusobacterium nucleatum, pks+ Escherichia coli and enterotoxigenic Bacteroides fragilis. These pathogenic bacteria produce toxins that can disrupt gut epithelial integrity resulting in heightened pro-inflammatory response, enhanced DNA mutations, and increased cell proliferation, which can eventually lead to adenoma formation. In addition, these bacterial pathogens show increased genotoxicity by forming invasive polymicrobial biofilms, thereby resulting in CRC development. Recently it has been reported that anatomical location plays a crucial role in CRC development, progression, microbial colonization, response to therapies and disease outcome. Indeed, right-sided CRC is generally associated with pro-oncogenic bacterial biofilms and is known to have an overall worse prognosis compared to left-sided CRC. Pathogenic bacteria use quorum sensing (QS) machinery in the gut for their communication, which is essential for biofilm formation. We aim to develop an intervention strategy employing QS machinery to engineer a probiotic bacterial strain with sensing and killing properties to detect and target these pro-oncogenic polymicrobial biofilms. The sensor device will detect autoinducers produced by pathogenic bacteria on encountering their biofilms, activating the killing device. The killing device expresses a biofilm degrading enzyme, Dispersin B, which will disrupt these biofilms and eventually kill the pathogenic bacteria residing in these biofilms by the type VI secretion system. These polymicrobial biofilms can act as a marker of CRC and help to understand the role of CRC-associated pathogenic bacteria in CRC development, which can eventually serve as a basis for developing future strategies for the diagnosis and treatment of CRC and other intestinal disorders associated with biofilms formed by pathogenic bacteria.

Оригинален текст от CORDIS (на английски).

Участници

EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergКоординаторГермания