Hidden Secrets of The Ribosome How to Hijack Sporulation in Bacteria

Much to the dislike of germaphobes, bacteria are everywhere, around and inside us. They account for nearly 3% of our body mass and are necessary for healthy digestion or immunity – they are our best weapon to fight their pathogenic cousins. The popular phrase ‘gut feeling’ may have more scientific basis that we realise as bacteria are linked to health of the nervous system and imbalance of the bacterial composition of our bodies is pointed to having a role in neurodegenerative diseases like multiple sclerosis.

Among bacteria, there is a unique group of ultimate survivors. Such bacteria can transition into spores – very hard, coated structures, which are widely found in soil, on fruits and vegetables, on any surfaces especially in food containers. Since spores can survive most of the processes used for sterilisation, including heat, radiation, chemical treatment, high pressure, they are an increasing burden in food processing and in hospitals. The most infamous members of the sporulating bacteria are two species of Bacillus and one species of Clostridium. Bacillus anthraxis poses a threat of being used as a bioterrorism weapon, while Bacillus cereus significantly contributes to food poisoning cases, especially from increasingly more popular ready-made meals. Clostridium difficile is recognised by World Health Organisation as a serious threat – it causes serious intestinal inflammation leading to colitis, colon perforation, sepsis and even death. Only a few C. diff spores are enough to infect a person whose gut bacteria composition is compromised by prolonged antibiotic therapy or an abuse of anti-reflux medication. C. diff infections are on a rise in hospitals.

Studying Bacillus subtilis, a species closely related to pathogens but harmless to humans, provides a powerful model to tackle infections caused by spore-forming bacteria. While the sequence of events necessary to form a spore is well established and carries a lot of similarities between all bacteria having such abilities, the rise of novel high-throughput methods allowing to monitor even the tiniest change in bacteria opens up the possibilities to find novel regulatory mechanisms behind this process.

The instructions for every living cell are written into DNA sequence. To be able to read this information, the DNA is transcribed into RNA molecules, which are templates forproteins, essential for every living organisms. At the heart of protein synthesis process stands a ribosome.

For decades ribosomes – a huge macromolecule called sometimes a nanomachine – were considered homogeneous entities, and for long not considered to play an active role in protein translation regulation.

Recently, a concept of ‘specialised ribosomes’ is gaining popularity within the scientific community. It assumes that not all ribosomes in the cell are the same and that subtle differences in the structure of this macromolecule may change their propensity to recognise RNA templates which in turn will change the copy number of newly synthesised proteins in the cell. Finding the proof of the hypothesis will mean discovering a new level of gene expression regulation and will open the door to possible modifications of translation machinery. In bacteria, imbalanced protein synthesis leads to accumulation of toxic intermediates which can induce bacterial cell death.

Understanding bacteria gives opportunities to find their weaknesses, which can be used to hijack the sporulation process and lead to the design of novel antibiotics.

About the Author

Agata StarostaAgata Starosta: After completing my Master degree at Jagiellonian University I moved to Munich to start a PhD at Ludwig-Maximillians University in Munich in the lab of dr. Daniel Wilson. I studied mechanisms of action of various antibiotics inhibiting protein synthesis. Soon after receiving my doctor degree, I was awarded an AXA Research Post-doc Fellowship to work on the role of translational elongation factor P. Lately, as a Marie Skłodowska-Curie Fellow, I moved to the lab of Jeff Errington at Newcastle University (UK) to work on sporulation in B. subtilis. This experience resulted in new ideas, which I will continue in my own group at Maria Curie-Skłodowska University in Lublin as a FIRST TEAM grantee.

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