Bacteria free themselves with molecular 'speargun'

June 16, 2017
Macrophage infected with Francisella novicida (magenta) assembles a dynamic nano-speargun (green). Credit: University of Basel, Biozentrum

Many bacteria are armed with nano-spearguns, which they use to combat unwelcome competitors or knockout host cells. The pathogen responsible for tularemia, a highly virulent infectious disease, uses this weapon to escape from its prison in cells defending the host. Researchers from the Biozentrum of the University of Basel report on this bacterial strategy in the current issue of Nature Communications.

Tularemia is an infectious disease that mostly affects rabbits and rodents, but also humans can become infected. The cause of this serious disease is the bacterium Francisella tularensis. The infection biologists led by Prof. Marek Basler and Prof. Petr Broz, from the Biozentrum of the University of Basel, demonstrate on a Francisella subspecies which is harmless to man, how these bacteria escape from digestive vesicles in defense cells using a nano-speargun.

Tularemia: a serious infectious disease

This zoonotic disease can spread to humans mainly through parasites such as ticks and fleas or by airborne infection. Without medical treatment, the can be fatal. "The mortality rate can be as high as thirty percent," explains Broz. "Inhaling as little as a dozen Francisella bacteria is sufficient to get infected." Since the pathogen is highly contagious and can spread rapidly through the air it has been included in the arsenal of biological weapons.

Pathogen has its own "weapon"

The bacterium Francisella, however, has an efficient "weapon" of its own - the so-called type VI secretion system (T6SS) - which basically works like a spear gun. The bacterium uses this nano-machine to escape from their "prison" in the phagocytes. These defense "ingest" that invade the body, enclosing them in small vesicles and digest them completely. However, by using the T6SS, Francisella disrupts these digestive vesicles and escapes into the cytosol, an environment where it can rapidly replicate.

Molecular speargun to escape from "prison"

The two research groups have now investigated the assembly and function of the T6SS in Francisella. In their study they have shown that the pathogen recycles its weapon. "After firing the speargun, it is immediately disassembled into its individual components. The bacterium then uses these components again to assemble a new T6SS," says Basler. "With this weapon, the bacteria puncture the vesicle membrane, in which they are enclosed, and deliver toxic proteins into the cytosol of the immune cell."

These so far uncharacterized effectors then disrupt the vesicle. This enables the bacteria to escape from their "imprisonment" and prevent their digestion. If they lack these effector proteins, they have no chance of escape. The T6SS as well as the toxic proteins are important virulence factors, as they are crucial e for the bacterium's success in an infection. Once the bacteria reach the cytosol, the fight is not yet over, as they need to successfully evade recognition and elimination by powerful innate immune responses.

Explore further: Bacteria supply their allies with munitions

More information: Maj Brodmann et al, Francisella requires dynamic type VI secretion system and ClpB to deliver effectors for phagosomal escape, Nature Communications (2017). DOI: 10.1038/ncomms15853

Related Stories

Bacteria supply their allies with munitions

September 8, 2016

Bacteria fight their competitors with molecular spear guns, the so-called Type VI secretion system. When firing this weapon they also unintentionally hit their own kind. However, as Prof. Marek Basler from the Biozentrum ...

What makes Francisella such a bad actor?

November 9, 2016

Scientists are gaining an insider's look behind the notorious infectivity of Francisella tularensis. This bacterium is an equal opportunity pathogen. It causes the disease tularemia in humans, rabbits and rodents, among others.

Francisella tularensis: Stopping a biological weapon

July 28, 2008

Scientists hope a vaccine is on the horizon for tularemia, a fatal disease caused by the pathogen Francisella tularensis, an organism of concern as a potential biological warfare agent. Until recently we knew very little ...

DNA markers distinguish between harmless, deadly bacteria

December 19, 2016

The virulent pathogen that causes the disease tularemia, or "rabbit fever," was weaponized during past world wars and is considered a potential bioweapon. Through a new study of the coccobacillus Francisella, Los Alamos National ...

Study gives clues about how deadly bacterium gains foothold

December 19, 2006

How a potentially deadly bacterium that could be used as a bioterrorist tool eludes being killed by the human immune system is now better understood, University of Iowa researchers report in the December issue of the Journal ...

Recommended for you

New hermit crab uses live coral as its home

September 20, 2017

A new hermit crab species can live in a walking coral's cavity in a reciprocal relationship, replacing the usual marine worm partner, according to a study published September 20, 2017 in the open-access journal PLOS ONE by ...

The right way to repair DNA

September 20, 2017

Is it better to do a task quickly and make mistakes, or to do it slowly but perfectly? When it comes to deciding how to fix breaks in DNA, cells face the same choice between two major repair pathways. The decision matters, ...

Barn owls found to suffer no hearing loss as they age

September 20, 2017

(Phys.org)—A small team of researchers with the University of Oldenburg has found that barn owls do not suffer hearing loss as they get older. In their paper published in Proceedings of the Royal Society B, the group describes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.