To split or not to split: how do bacteria decide?
Oeiras, 26 September 2023
When reproducing, bacteria grow and duplicate their genetic material. Then, they form a cell wall in the middle, the division septum, which splits to give rise to two daughter cells. If pathogenic bacteria happen to split too soon, they might expose an immature cell surface, lacking the virulence factors which allow them to evade the immune system. As a consequence, they would be cleared from the infected host.
The bacterial pathogen Staphylococcus aureus (S. aureus) is best known for its multi-resistant form, which is the second major cause of death by antibiotic resistant infections, as it caused more than 700000 deaths in 2019. Its splitting process is controlled by a group of proteins that cut through the septal cell wall, as a pair of scissors, in less than two milliseconds. One of these proteins is Sle1.
Researchers at the Instituto de Tecnologia Química e Biológica António Xavier (ITQB NOVA) have just uncovered a new mechanism through which bacteria avoid premature division. The discovery, published in The EMBO journal, links two important but distant steps of the cell cycle.
The Bacterial Cell Biology lab, led by Mariana Pinho, found that, when it is time for the cell to divide, a protein involved in chromosome segregation, known as FtsK, acts as a gatekeeper and informs Sle1 that it is time to cut through the septal cell wall. When the research team deleted FtsK, they could no longer find Sle1 in the bacteria, which could no longer properly split.
But why does FtsK, which acts in the early cell cycle process of chromosome segregation, control the levels of Sle1, involved in the late event of daughter cell separation?
“FtsK acts as a checkpoint, only allowing cell splitting when the chromosomes are correctly segregated, and no longer at the division site”, explains Helena Veiga, a researcher at ITQB NOVA and first author of the paper. “If chromosome segregation is compromised or if there is DNA damage, FtsK will signal it and prevent premature cell splitting”.
“This research is important to understand how an important bacterial pathogen controls the correct timing of cell division while in a test tube or inside an infected host” says Mariana G. Pinho. "Our ultimate goal is to contribute with knowledge that will help us fight infections by this deadly pathogen”, the researcher concludes.
Original Paper
The EMBO Journal
Cell division protein FtsK coordinates bacterial chromosome segregation and daughter cell separation in Staphylococcus aureus
Helena Veiga, Ambre Jousselin, Simon Schäper, Bruno M Saraiva, Leonor B Marques, Patricia Reed, Joana Wilton, Pedro M Pereira, Sérgio R Filipe, Mariana G Pinho
DOI: https://doi.org/10.15252/embj.2022112140
This study was funded by the European Research Council, national funds through FCT– Fundação para a Ciência e a Tecnologia, the Swiss National Foundation, the European Union’s Horizon 2020 research and innovation programme and the European Molecular Biology Organization.
