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Winter 2016

How bacterial predators kill other bacteria without harming themselves

Copyright: Liz Sockett
  • Bacteria-killing bacteria (“predatory bacteria”) may assist humans in fighting pathogens in the post-antibiotic era
  • How predatory bacteria function has been little understood to date
  • Predators have been found to produce a protein “antidote” that protects them from their own weapons
  • Self-protection technique allows one bacterium to destroy others
  • The findings offer clues to how bacterial predation may have first evolved
  • Understanding how these predators attack bacteria could provide new ways of combatting antimicrobial resistance

A joint study by the labs of Dr Andrew Lovering and Prof Liz Sockett, at the Universities of Birmingham and Nottingham, has shown how predatory bacteria protect themselves from the weapons they use in their bacterial killing pathway. The research, published in Nature Communications, offers insights into early steps in the evolution of bacterial predators and will help to inform new ways of combatting antimicrobial resistance.

A useful predatory bacterium called Bdellovibrio bacteriovorus eats other bacteria (including important pathogens of humans, animals and crops). It attacks them from inside out using enzymes (called DD-endopeptidases) that first loosen the cell walls of prey bacteria and then cause them to round up like a pufferfish, providing space as a temporary home for the predator. However, Bdellovibrio also have similar cell walls so why don’t they fall victim of their own attack?

Video

The project, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), found that the bacterium uses an ankyrin-type protein called Bd3460 as a shield. It binds to the tip of the enzyme weapons, nullifying their action until they are safely secreted out of the Bdellovibrio and into the prey bacteria.

Dr. Andrew Lovering and Ian Cadby at the University of Birmingham determined the structure of the ankyrin protein using X-ray crystallography and found that that it attaches to two DD-endopeptidase weapons to temporarily deactivate them.

“When I first showed this to Liz, she hit the nail on the head by describing it as a decorative “quiff” on top of the endopeptidase” said Dr Lovering. “This covers up the active site of the enzymes that are used to cut cell walls and offers protection to the Bdellovibrio until these weapons are excreted into the prey.”

Copyright: Liz Sockett
Top: Wild type Bdellovibrio typically arrive at (larger) E.coli bacteria then secrete wall-acting enzymes, invade them. Ankyrin protects them from the action of their own secreted enzymes. Bottom: Ankyrin- minus mutant Bdellovibrio arrive at (larger) E. coli then secrete wall-acting enzymes. Protective ankyrin is missing so Bdellovibrio round their own walls up instead and can’t invade. Copyright: Liz Sockett

Carey Lambert, Rob Till and Prof Liz Sockett at The University of Nottingham confirmed the antidote protein’s use when the gene responsible for its production was deleted.

Prof Liz Sockett said: “When the Bd3460 gene responsible for antidote production was deleted, the Bdellovibrio had no way of protecting itself from its own weapons. When it attacked harmful bacteria with its cell-wall-damaging enzymes it also felt the effects.

“The Bdellovibrio bacteria lacking the Bd3460 gene tried to invade the bacteria but suddenly rounded up like pufferfish and couldn’t complete the invasion – the fatter predator cell could not enter the prey cell.”

This is the first paper to discover a ‘self-protection’ protein in predatory bacteria.

Prof Liz Sockett added, “Most bacteria are not predatory and so understanding these mechanisms gives us a glimpse of how predation evolved. In this case it seems that the Bd3460 gene was transferred into ancestors of Bdellovibrio, probably when they were beginning to develop as predators.”

Commenting on the potential impact of the study, Dr Andrew Lovering added: “If we are to use Bdellovibrio as a therapeutic in the future, we need to understand the mechanisms underpinning prey killing and be sure that any self-protective genes couldn’t be acquired by pathogens, causing resistance. Brilliantly, Liz and Carey have demonstrated this did not happen with the bd3460 antidote protein, and Ian and I showed how the mechanism works on predator enzymes only – this is a great inter-university collaboration.”

ENDS

Notes to editors

Reference: Ankyrin-Mediated Self-Protection During Cell Invasion by the Bacterial Predator Bdellovibrio bacteriovorus, Nature Communications. DOI: 10.1038/NCOMMS9884

BBSRC is one of the UK Research Councils. The Research Councils, led by the Medical research Council, are working on a joint Antimicrobial Resistance (AMR) Programme to find new ways to kill infectious pathogenic bacteria that are drug-resistant. Bdellovibrio is a natural predator and understanding the mechanisms it requires for successful predation provides vital knowledge towards these aims.

Figures:
Electron Micrographs of puffed-up mutant & normal Bdellovibrio predators
Structure of DD-endopeptidase in complex with Ankyrin

About The University of Nottingham

The University of Nottingham has 43,000 students and is ‘the nearest Britain has to a truly global university, with campuses in China and Malaysia modelled on a headquarters that is among the most attractive in Britain’ (Times Good University Guide 2014). It is also one of the most popular universities in the UK among graduate employers and the winner of ‘Research Project of the Year’ at the THE Awards 2014. It is ranked in the world’s top 1% of universities by the QS World University Rankings, and 8th in the UK by research power according to REF 2014.

The University of Nottingham in Malaysia (UNMC) is holding events throughout 2015 to celebrate 15 years as a pioneer of transnational education. Based in Semenyih, UNMC was established as the UK's first overseas campus in Malaysia and one of the first world-wide.

Impact: The Nottingham Campaign, its biggest-ever fundraising campaign, is delivering the University’s vision to change lives, tackle global issues and shape the future.

About BBSRC

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

Funded by Government, BBSRC invested over £509M in world-class bioscience in 2014-15. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.

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