Breaking Symmetry: how spherical bacteria organize their DNA for survival
When propagating, bacteria grow, duplicate their content, and then split in two, with each daughter cell receiving a complete copy of the genetic material. This process is precisely organized in time and space to guarantee that the genetic information is correctly passed on to the next generations.
Most of our knowledge about this aspect of the bacterial biology comes from a selected group of rod-shaped organisms, which always divide by cutting straight across their middle. But this is not the case for Staphylococcus aureus (S. aureus), which is spherical and divides along different, perpendicular directions over sequential division cycles.
At ITQB NOVA’s Bacterial Cell Biology lab, led by Mariana G. Pinho, researchers are particularly interested in this bacterium, not only because it has a different shape and way of dividing, but also because it is the second major cause of death by antibiotic resistant infections worldwide. Studying this pathogen’s biology is essential to develop innovative strategies against it.
Most bacteria carry their genes on a single circular chromosome, which has a starting point (the origin) and an ending point (the terminus). During cell division, the DNA is copied, much like unzipping a zipper, from the origin in both directions around the circle until the two sides meet at the terminus, ensuring each new cell receives a complete set of instructions.
In their most recent study, published in Nature Communications, the research team followed the localization and movement of chromosomes during S. aureus division, revealing new details about this process. “We found that newborn cells usually start with two chromosome origins positioned at opposite cell poles, near the membrane, while the chromosomes’ terminus stay at the center, leading to a longitudinal arrangement”, explains Adrian Izquierdo Martinez, ITQB NOVA researcher and co-first author of the paper. “This creates a clear axis guiding where the division machinery, which will cut this mother cell in two, will assemble”, he adds.
The researchers also studied how key proteins contribute to this process. They found out that ParB, a protein that is central to chromosome segregation in various bacteria, including S. pneumoniae, the primary cause of community-acquired pneumonia, only plays a minor role in S. aureus. Its main task is to recruit a complex called SMC, which, in contrast, is really needed for chromosome segregation. “When we removed SMC or its partner proteins from the cells, they frequently failed to inherit DNA correctly, leading to up to one sixth of cells lacking genetic material”, reveals Simon Schäper, ITQB NOVA researcher and co-first author of the paper. Together, these mechanisms enable spherical bacteria to keep their chromosomes organized and to segregate them accurately, even without obvious geometric cues.
Although many of the techniques the researchers used to get to these results had already been used in other organisms, some had never been adapted to work in S. aureus. “Now that we have a good toolset to study the chromosome dynamics of S. aureus, we can use it to discover new factors involved in this process”, explains Mariana G. Pinho, principal investigator at ITQB NOVA. “We can also employ these tools to uncover how the genetic material is organized during stress conditions or during infection and how this can impact antibiotic resistance”, she concludes.
The study was developed in collaboration with the Indiana University.
European Research Council through ERC Advanced Grant 101096393 (to MGP), La Caixa Foundation grant HR23-00221 (to MGP), Fundação para a Ciência e a Tecnologia (FCT) through grant 2022.01678.PTDC (to SS) and contract 2022.03033.CEECIND (to SS), MOSTMICRO-ITQB R&D Unit (UIDB/ 04612/2020, UIDP/04612/2020 to ITQB-NOVA) and LS4FUTURE Assoiated Laboratory (LA/P/0087/2020 to ITQB-NOVA), and National Institutes of Health R01GM141242, R01GM143182, and R01AI172822 (to X.W.). Research is a contribution of the GEMS Biology Integration Institute, funded by the National Science Foundation DBI Biology Integration Institutes Program, Award #2022049 (X.W.).
