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

Project description

Hitting bacteria where it hurts

Staphylococcus aureus is a common bacterium that might very well be living on your skin or in your nose but causing no harm. However, these bacteria can turn deadly if they find their way into your bloodstream, joints, bones, lungs, or heart. Staph infections cause food poisoning, septicaemia, toxic shock syndrome, and even septic arthritis. Notorious for its ability to become resistant to antibiotics, Staphylococcus aureus is an excellent model system to elucidate the mechanisms of antibiotic tolerance. CheckBacZ is using high-tech methods to evaluate the different stages of this bacteria's cell cycle to find ways to make them vulnerable to drugs.

Objective

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.

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Coordinator

UNIVERSIDADE NOVA DE LISBOA
Net EU contribution
€ 147 815,04
Address
Campus de campolide
1099 085 Lisboa
Portugal

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Region
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00