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Checkpoints in the bacterial cell cycle: role of the cytokinetic Z-ring and implications for antibiotic resistance

Descripción del proyecto

Golpear a las bacterias donde duele

«Staphylococcus aureus» es una bacteria común que podría vivir perfectamente en nuestra piel o nariz sin provocar ningún daño. Sin embargo, estas bacterias pueden resultar mortales si logran entrar en el torrente sanguíneo, las articulaciones, los huesos, los pulmones o el corazón. Las infecciones por estafilococo provocan intoxicación alimentaria, septicemia, síndrome del choque tóxico e incluso artritis infecciosa. Muy conocida por su capacidad de adquirir resistencia a los antibióticos, «Staphylococcus aureus» es un sistema modelo perfecto para esclarecer los mecanismos de la tolerancia a los antibióticos. CheckBacZ está utilizando métodos de alta tecnología para evaluar las distintas fases del ciclo celular de estas bacterias con el fin de encontrar formas de hacer que sean vulnerables a los fármacos.

Objetivo

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.

Coordinador

UNIVERSIDADE NOVA DE LISBOA
Aportación neta de la UEn
€ 147 815,04
Dirección
CAMPUS DE CAMPOLIDE
1099 085 Lisboa
Portugal

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Región
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 147 815,04