CheckBacZ · Checkpoints in the bacterial cell cycle: role of the cytokinetic Z-ring and implications for antibiotic resistance
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2020-09-01 → 2022-08-31
- Финансиране от ЕС
- 147 815 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Механизмите за делене на бактерията Staphylococcus aureus се анализират чрез изследване на т.нар. Z-пръстен, който контролира изграждането на новата клетъчна стена. Познаването на тези процеси помага за разработването на нови стратегии за борба с антибиотикорезистентните щамове.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Checkpoints in the bacterial cell cycle: role of the cytokinetic Z-ring and implications for antibiotic resistance
The occurrence of multiple-drug resistant bacteria constitutes an important threat to healthy lives. The clinically relevant pathogen Staphylococcus aureus is a major concern because of the emergence of methicillin-resistant S. aureus (MRSA) strains that cause life-threatening disease in humans. In 2019, MRSA was the second most common cause of global deaths associated with bacterial antimicrobial resistance. To efficiently combat difficult-to-treat infections in the future, the development of alternative strategies will be necessary, which require fundamental knowledge about essential processes in bacteria. The project CheckBacZ addressed basic cell biology questions about regulatory mechanisms for the cell cycle and their implications for antibiotic resistance of the bacterial pathogen S. aureus. The bacterial cell cycle can be described as a series of coordinated events leading to cell proliferation. Despite overlapping cell cycle events in bacteria, several lines of evidence suggest the existence of so-called checkpoints that ensure an orderly progression through the cell cycle. In particular, this project aimed to elucidate mechanisms for the initiation and control of the synthesis of the division septum, which starts with the assembly of the so-called Z ring, made of filaments of the bacterial tubulin homologue FtsZ and its membrane anchors. The Z ring then recruits later divisome proteins, including proteins involved in peptidoglycan biosynthesis, which will synthesize the cell wall, essential for cells to divide. Relatively little is known about what controls the timing of Z-ring assembly, the rate of cytokinesis or the organisation of the cell wall synthesis machinery to drive the coordinated synthesis of the septum. The results of this project have contributed to our understanding of mechanisms underlying both the synthesis and splitting of the division septum and hence promoting cell cycle progression in S. aureus. In the long term, we hope these results contribute to uncover new targets for antibiotics to open new possibilities for counteracting difficult-to-treat bacterial infections.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The occurrence of multiple-drug resistant bacteria constitutes an important threat to healthy lives, signifying the importance of alternative strategies to combat bacterial infections. This research project bears the potential to significantly contribute to overcome antibiotic resistances that occur during the treatment of bacterial infections, as it combines the studies of cell division, cell cycle regulation and antibiotic resistance in the clinically relevant model Staphylococcus aureus. Given that the tubulin homologue FtsZ is essential for cell division and serves as an antibiotic resistance determinant in this organism, the proposed research activity focuses on the cytokinetic Z-ring, more precisely its role in driving the staphylococcal cell cycle. Super-resolution microscopy will be used to determine if FtsZ treadmilling controls the rate of cytokinesis and if it organizes the peptidoglycan synthesis proteins during cell division, aiming to provide evidence for a FtsZ-dependent checkpoint in the cell cycle. Profiting from a mutant screen currently ongoing in the host laboratory, mutants impaired in the timing of septum formation will be identified to study the functional integration of corresponding genes into FtsZ-driven septum synthesis. In view of the fact that bacteria at different stages of the cell cycle are phenotypically distinct, microfluidics will be used to test if the degree of antibiotic tolerance varies during the cell cycle, which would enforce the vision for re-sensitizing resistant bacteria by manipulating their cell cycle. The strong expertise and the availability of cutting-edge techniques in the host group together with my professional experience will generate an ideal synergy within this work programme. I will generate valuable scientific knowledge, acquire transferrable skills and create new collaborations in the international bacterial cell biology community, thus paving the way for establishing myself as an independent researcher.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSIDADE NOVA DE LISBOA · LisboaКоординаторПортугалия
Връзки
Данни: CORDIS, © Европейски съюз