The bony human skeleton needs little introduction: it holds our shape and allows us to go through our motions and activities. Though the importance of the human skeleton is clear, what may be surprising is that bacteria—tiny organisms visible only with a microscope—also have skeletons. Much as in humans, the bacterial skeleton, or “cytoskeleton,” is essential for holding the shape of a bacteria—whether round, rod-shaped, or spiral-shaped—and is also vital to bacterial activities, the most familiar of which are in causing disease and infection, but can also include production of food, manufacture of medicines, and environmental cleanup [1,2].

If the idea of a bacterial skeleton is surprising, you are not alone. Even scientists in the field doubted the existence of the bacterial cytoskeleton until about 20 years ago. When the bacterial cytoskeleton was discovered in the 1990s, it dramatically changed the way scientists thought about bacteria and generated new research questions that have been under investigation ever since [2,3]. This present and future work will have practical applications, such as the development of antibiotics, and may help scientists unlock the inner workings not just of bacteria but of other organisms—even humans [3,4].

So what is the cytoskeleton, anyway?

The building block of all living things—from bacteria, to plants, to animals and humans—is the cell. Roughly speaking, cells are membrane-enclosed units that contain organized mixtures of biological materials, which include but are not limited to proteins, fats, and DNA (Figure 1). Among these components is the cytoskeleton, a system of protein fibers that provides structure and support to the cell (Figure 1).

Figure 1 ~ The cytoskeleton provides structure and support to cells, the biological building block. Cells are organized mixtures of biological materials that make up all organisms, including humans and animals (top). Using microscopy, individual cytoskeletal fibers can be observed (bottom). Two types of cytoskeleton fibers, known as microtubules and actin, are shown in green and red, respectively. The blue structure represents a separate component of the cell, called the nucleus. (Image credit: Wikimedia Commons user Jan R.)

Decades before the bacterial cytoskeleton had been discovered, scientists were already investigating the cytoskeleton in eukaryotes, the group of organisms that includes familiar life-forms such as plants and animals. These studies in eukaryotes revealed that cytoskeleton protein fibers are made up of smaller, repeating protein units that undergo addition or removal, resulting in overall increases or decreases in fiber length (Figure 2).

Figure 2 ~ The structure of the cytoskeleton. In both eukaryotes (blue, left) and bacteria (violet, right), the cytoskeleton is made up of smaller, repeating protein units that add together to form fibers. Once these fibers are formed, they can continue to grow or shrink through addition or removal of subunits. In eukaryotes, subunits called tubulin add together to form microtubule fibers, while in bacteria, a similar subunit called FtsZ form the FtsZ fibers. Adapted from Wickstead B, Gull K (2011) J Cell Biol 194: 513-25.

The cytoskeleton and the cell: a drawstring on a purse

A major role of the cytoskeleton in both eukaryotic and bacterial cells is in the process of cell division, which is key to the growth and survival of all organisms [5]. As the name suggests, this process involves the dividing of a single parent cell into two new daughter cells. The cytoskeleton performs a variety of tasks throughout this process of cell division, but one particularly interesting function is in forming a ring around the middle of the parent cell. This cytoskeleton ring drives the physical splitting of parent cells into the two daughters, a process known as cytokinesis [5].

One way to picture this is to imagine the parent cell as a purse, which is encircled by a drawstring that is the cytoskeleton. When the cytoskeleton “drawstring” around the parent cell “purse” is tightened, the cell constricts until only a thin neck connects the two halves of the parent. At this point, the cell can be severed at this neck, creating two new daughter cells (Figure 3).

Figure 3 ~ The role of FtsZ in cell division in bacteria. During cell division, a single parent cell grows in size and forms a FtsZ “drawstring” (violet) that encircles the cell down its middle. Constriction of the FtsZ drawstring through the removal of FtsZ subunits helps to physically separate the dividing cell into two new daughter cells. Adapted from Wickstead B, Gull K (2011) J Cell Biol 194: 513-25.

How can these microscopic fibers function as a drawstring? Research in the last few years has already suggested that in bacteria, a specific type of cytoskeleton protein known as FtsZ constricts the parent cell [6]. With recent improvements in microscopy techniques, scientists have been able to observe that constriction of the FtsZ drawstring occurs simultaneously with the removal of individual FtsZ units from the fiber [6]. These observations strongly point towards pinching of the dividing bacteria by FtsZ as a consequence of the “shrinkage” of the drawstring.

Very recently, a study published in December 2013 by researchers at Harvard University uncovered yet another layer in the story of the FtsZ drawstring [7,8]. This study indicated that the “shrinkage” of FtsZ depends on another protein known as FtsA [7,8]. In the past, FtsA was known to be required for cell division by helping FtsZ subunits get to the correct location so that the FtsZ drawstring can form [7,8]. The recent study highlights a new role for FtsA, in which it helps to remove FtsZ subunits to enable the constriction of the FtsZ drawstring [7,8]. Thus, while FtsA and FtsZ were both known to be involved in cell division, this finding is striking because it points towards a way which the two proteins work together that was previously unknown [7,8]. The discovery of this interaction may point towards many more layers of complexity in this process that remain to be uncovered.

Broader importance: from bacteria, to mice, to humans

Studies of FtsZ, bacteria, and the cytoskeleton may all seem to have abstract, distant importance. However, from a practical standpoint there are a variety of reasons to be interested in these types of research questions.

Perhaps the most intuitive relevance of this research is in health applications, such as in developing antibacterial strategies. About 10 years ago, scientists first discovered chemicals that target FtsZ [4,6]. Such compounds can disrupt bacterial cell division by blocking the removal of FtsZ subunits, thereby preventing necessary shrinkage of FtsZ fibers, as well as by preventing the formation of a FtsZ drawstring in the first place [4]. Though these chemicals were not adaptable to human use when first discovered, over the last 5-6 years, scientists have focused on improving anti-FtsZ strategies. Through these efforts, researchers have now achieved effective use of these compounds against bacterial infections in mice [4,6]. While much more testing will be needed before FtsZ drugs can be used against human bacterial disease, this success in mice is a promising sign that a better understanding of the bacterial cytoskeleton is a powerful tool in human healthcare.

In addition to these promising applications towards disease, this research also has less tangible yet nonetheless intriguing long-term impacts. Studying the bacteria cytoskeleton provides insights not just into bacteria, but also into the cytoskeletal proteins and structures belonging to eukaryotes, including humans. By understanding the similarities and differences between bacterial and eukaryotic cytoskeletons, scientists can better understand the functions and processes of these proteins in organisms closer to humans, and in ourselves. Furthermore, these studies can also illuminate evolutionary relationships and make it possible to better trace the ancestors from which modern-day organisms originated [4].

Thus, while at first glance the skeletons of bacteria may not seem to have obvious connections to ourselves, a deeper look at the field points towards the numerous ways in which research at the microscopic level can have great influences on human life.

Vivian Chou is a PhD student in the Harvard Biological and Biomedical Sciences Program.

References

[1] Graumann PL (2009) Dynamics of bacterial cytoskeletal elements. Cell Motil Cytoskeleton 66:909-14.

[2] Wickstead B, Gull K (2011) The evolution of the cytoskeleton. J Cell Biol 194: 513-25.

[3] Nath D (2008) Milestone 21: The bacterial cytoskeleton. Nature. http://www.nature.com/milestones/milecyto/full/milecyto21.html

[4] Sass P, Brötz-Oesterhelt H (2013). Bacterial cell division as a target for new antibiotics. Curr Opin Microbiol 16:522-530.

[5] O’Connor C. (2008) Cell Division: Stages of Mitosis. Nature Education. http://www.nature.com/scitable/topicpage/mitosis-and-cell-division-205

[6] Erickson HP, Anderson DE, Osawa M. (2010) FtsZ in bacterial cytokinesis: cytoskeleton and force generator all in one. Microbiol Mol Biol Rev 74:504-28.

[7] Loose M, Mitchison T (2013) The bacterial cell division proteins FtsA and FtsZ self-organize into dynamic  cytoskeletal patterns. Nat Cell Biol 16:38-46.

[8] Du Toit A (2013) Remodelling the FtsZ network. Nat Rev Microbiol 12:77.

 

Links of interest

[1] Cell Size and Scale  http://learn.genetics.utah.edu/content/cells/scale/

[2] McGraw Hill animation on cytokinesis. http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter10/animation_-_cytokinesis.html

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