Imaging bacteria in space and time

Issue #31; Summer 2019

A recent technological advance combined with a new model organism allow us to see the complex dynamics of cell division in Streptomyces.

To grow and propagate every cell must divide. One of the key questions in fundamental research is to understand how bacteria determine where and when to divide. Despite much research into how many traditional model bacteria divide, little is known about cell division in Streptomyces, the soil-dwelling bacteria best known as prolific producers of many of the antibiotics in clinical use today.

These bacteria have an intriguing and complex multicellular life cycle during which they grow as long branching filaments like fungi, and multiply by producing spores. Importantly, antibiotic production, growth and the timing of spore formation are tightly coordinated processes within the Streptomyces life cycle.

Recent advances in imaging the Streptomyces life cycle pioneered by Dr Susan Schlimpert have transformed the ability to study the molecular basis of growth and cell division in Streptomyces. The new approach takes a sequence of images of an organism under the microscope over a period of time, known as time-lapse microscopy. To ensure optimal growth conditions, the organism being studied is maintained in a small chamber (microfluidic plate) and is constantly supplied with nutrients.

To complement the time-lapse microscopy, proteins can be fluorescently tagged and then recorded throughout the life cycle, offering the ability to follow what proteins do in time and space. Dr Schlimpert explains, “You don’t just want to see a snap-shot of a dynamic process that takes several hours, but capture the entire event while bacteria are happily growing and dividing.”

The other technological advance is the development of a new model organism, Streptomyces venezuelae, which grows and divides in liquid. “The traditional model organism for this bacterial species, Streptomyces coelicolor only divides and produces spores when it is grown on solid media” points out Dr Schlimpert. “In addition, the length and complexity of the three-dimensional growth pattern of S.coelicolor has made the time-resolved analysis of dynamic processes, like cell division, technically very challenging. Using the close relative S. venezuelea has allowed us to overcome all those challenges in imaging the complete Streptomyces life cycle, including filamentous growth and spore formation.”

Streptomyces venezulae as a model system was first developed by Professor Mark Buttner’s group, where Dr Schlimpert worked as a Postdoctoral Researcher before she started her own group earlier this year after being awarded a prestigious Royal Society Independent Research Fellowship.

Dr Schlimpert’s current focus is on understanding the spatio-temporal control of cell division and multicellular development in Streptomyces. One of the key questions is to understand how filamentous growing bacteria, like Streptomyces, determine when and where to divide.

Unlike most other bacteria which simply split in half, Streptomyces undergo a massive and unique cell division event that leads to the simultaneous formation of dozens of identical daughter cells called spores.

“It is absolutely fascinating to watch Streptomyces dividing under the microscope,” explains Dr Schlimpert, “because all of a sudden Streptomyces filaments that produce the key cell division protein FtsZ tagged with a yellow fluorescent protein will light up. In an almost synchronous event, this cell division protein will then accumulate in very discrete and regularly-spaced bands along the filaments – looking like a yellow ladder.

“These yellow bands will then lead to the formation of division walls that result in the production of tens of spores that can be released into the environment to restart the life cycle. We want to understand how the regular spacing of these FtsZ ladders is achieved at the molecular and cellular level.”

Studying cell division in Streptomyces in greater detail will provide new insights into the different mechanisms of bacterial cell division. Furthermore, Dr Schlimpert suggests that a holistic understanding of the biology of Streptomyces is likely to be beneficial for the development of new experimental approaches for the exploitation of Streptomyces to produce commercially and medically relevant molecules.

How to watch Streptomyces dividing under the microscope

  1. Unlike many other Streptomyces strains, S.venezuelae grows and divides into spores when grown in liquid medium
  2. S. venezuelae is placed under the microscope and cell division can be tracked in real time using fluorescence time-lapse microscopy. The culture medium in the microfluidic plate supplies nutrients
  3. Software collates the image series to create a movie of Streptomyces cell division, allowing scientists to follow fluorescently-tagged proteins (yellow) during Streptomyces growth and cell division

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