Research Summary: Our research demonstrates a novel mode of direct attachment to the membrane for the cell division protein FtsZ in a class of bacteria that lack cell wall and contain cholesterol in their membrane.
Author interview: Soumyajit Dutta is currently a PhD student at the Department of Biology, IISER Pune. He completed his bachelors and masters from IISER Kolkata and then joined IISER Pune to pursue PhD in structural biology in the lab of Dr. Gayathri Pananghat. Soumyajit’s research focuses on the structural aspects of bacterial cytoskeleton proteins involved in the cell division process.
Lab: Dr. Gayathri Pananghat, Indian Institute of Science Education and Research (IISER), Pune
What was the core problem you aimed to solve with this research?
Cell division (the process by which two daughter cells are formed from a mother cell) is a fundamental process in all living organisms for survival. Understanding the mechanism of cell division in bacteria, especially the disease-causing ones, can help us to discover novel strategies to stop the cell division process and eliminate them. Bacteria are very small (about ten thousand times smaller than a house fly), single celled organism where DNA (the genetic material) and cytoplasm (a jelly like material inside the cell) is surrounded by a membrane and a cell wall.
In some bacteria the cell wall is absent and mycoplasma is one such cell wall-less bacteria. Mycoplasmas are known to cause various diseases in humans and other animals. Majority of the antibiotics are against cell wall synthesis enzymes, and hence we have limited ammunition for tackling diseases caused by these cell wall-less bacteria. Till date most of the research about cell division is focused on the cell walled bacteria leaving the precise functions of division proteins in the wall-less class of bacteria poorly understood. My research aims to fill this gap and which is on certain proteins that take part in the cell division process in mycoplasma. A detail understanding of how these proteins function will reveal novel strategies for inhibiting cell division.
How did you go about solving this problem?
We first performed bioinformatics analysis (where we use various computational tools and software to understand complex biological data) to identify the presence and absence of cell division proteins FtsZ and FtsA across mycoplasma genomes. To note FtsZ and FtsA are two essential cell division proteins in cell walled bacteria and they are known to interact with each other. FtsA helps FtsZ ring to tether to the membrane and thus facilitates the constriction process. We looked at the specific sequence features of these proteins and predicted their functions. For example, we were interested in specific motifs in FtsZ that binds to FtsA. In cases where the FtsA binding motif is not present in FtsZ, we asked whether there exist alternative ways for membrane anchoring. Here, we discovered the presence of membrane binding motif by predicting the amphipathic parameters in FtsZs of a few mycoplasma species. Next, we performed in vitro experiments with purified proteins to check if our prediction is indeed valid and we demonstrated that Mycoplasma genitalium FtsZ is capable of binding membranes. Overall, in our research, we performed bioinformatics analysis accompanied by an in vitro experimentation approach to address our questions.
The discovery of mycoplasma FtsZ proteins that directly attach to membrane opens up many more questions on the diversity and evolution of constriction machinery in bacteria.
How would you explain your research outcomes (Key findings) to the non-scientific community?
In the current study, we have discovered a novel membrane binding and cholesterol interacting property of an essential cell division protein FtsZ of Mycoplasma genitalium bacterium. Earlier, FtsZ was thought to require different accessory proteins for anchoring to the membrane. Now the current experimental evidence of a direct membrane attachment and cholesterol interaction in FtsZ from our research opens new directions for exploring the novel mechanism of cell division and its clinical significance. Having said so, our present research has been carried out in an in vitro set-up, meaning, we have studied the proteins in an artificial laboratory system which is outside the cellular environment, which gives mechanistic details of protein function. Our future focus will be to conduct the study inside living organisms in a native state to further confirm our current findings.
What are the potential implications of your findings for the field and society?
In cell walled bacteria, FtsZ does not directly attach to the membrane. It requires anchor proteins like FtsA, ZipA, SepF etc. to go to the membrane. Our discovery of a direct membrane binding mode in mycoplasma FtsZ provides a new perspective to study novel functions of FtsZ and FtsA in cell division. The very fact that mycoplasmas are genome reduced bacteria where many genes are lost during evolution, it can be considered as a model system for studying a minimal division machinery. Mycoplasmas including M. genitalium and M. pneumoniae are known pathogenic agents to humans. Importantly, the absence of cell wall makes them naturally resistant to beta-lactam antibiotics that specifically target cell wall synthesis. The discovery of membrane binding and cholesterol interacting properties of an essential cell division protein FtsZ can lead to further studies on how these properties affect the division process. An in depth understanding of the mechanism can potentially lead to the discovery of novel strategies for inhibiting mycoplasma infection in future.
What was the exciting moment during your research?
The most exciting moment was when I performed the experiment to check membrane binding of the predicted motif of Mycoplasma genitalium FtsZ for the first time and came to see that it was indeed binding. This was quite exciting as bacterial FtsZs were not known to possess any membrane binding property according to earlier reports.
Paper reference: Dutta, S., Poddar, S., Chakraborty, J., Srinivasan, R., & Gayathri, P. (2025). Membrane Binding and Cholesterol Sensing Motif in Mycoplasma genitalium FtsZ: A Novel Mode of Membrane Recruitment for Bacterial FtsZ. Biochemistry. 2025 64 (8), 1864-1877. https://doi.org/10.1021/acs.biochem.4c00543
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