A nano-machine cell killer: Team deciphers the attack strategy of certain bacteria

Aug 04, 2013

This is a veritable mechanics of aggression on the nanoscale. Certain bacteria, including Staphylococcus aureus, have the ability to deploy tiny darts. This biological weapon kills the host cell by piercing the membrane. Researchers at EPFL have dismantled, piece by piece, this intriguing little machine and found an assembly of proteins that, in unfolding at the right time, takes the form of a spur. Published in Nature Chemical Biology, this discovery offers new insight into the fight against pathogens that are increasingly resistant to antibiotics.

To attack the host cell, the weapon must first attach. On the surface of the aggressor is a mechanism composed of seven proteins that are folded over and assembled into a ring. The researchers were able to show how, in time, these long molecules unfold to form a kind of spur.

The trigger is just another part of the machine – a peptide, or a small . When exposed to the enzymes of the , it detaches. The balance of the assembly adjusts: the proteins adopt a new form, spreading out in a circular motion to form a spur, which then pierces the membrane of the host cell.

Mechanical at the molecular level

No chemical reaction is involved in these biological weapons. This is a mechanical phenomenon, albeit on the molecular level. Matteo Dal Peraro, co-author of this study, also uses the term "nanomachine" to refer to this tool of aggression.

The EPFL researchers have worked on strains of Aeromonas hydrophila – a bacterium well-known among travelers for the intestinal disorders it causes. In Petri dishes the researchers could, at will, cause the formation of these darts, thereby exposing microorganisms to . They were able to model precisely how each protein dynamically rearranges, once the peptide is missing, to form the spur.

Hinder the attack mechanism

For co-author Gisou Van der Goot, this discovery opens new therapeutic perspectives, for example in cases of nosocomial infection staphylococci. "We could imagine catheters coated with substitute peptides," she says. "They could prevent the formation of the ring and, thus, the spur. We would avoid many hospital infections."

The concept is to address the weaponry of the bacteria rather than the bacteria itself. This is particularly attractive at a time when multiple antibiotic resistances are becoming increasingly common. "This approach would have the advantage of not causing mutations, and thereby resistance, in pathogenic bacteria," says the researcher.

Explore further: New tool identifies therapeutic proteins in a 'snap'

Related Stories

Chemists find new compounds to curb staph infection

May 23, 2013

(Phys.org) —In an age when microbial pathogens are growing increasingly resistant to the conventional antibiotics used to tamp down infection, a team of Wisconsin scientists has synthesized a potent new ...

Cell: Protein folding via charge zippers

Jan 18, 2013

Membrane proteins are the "molecular machines" in biological cell envelopes. They control diverse processes, such as the transport of molecules across the lipid membrane, signal transduction, and photosynthesis. ...

Study reveals secrets of bacterial slime

Apr 12, 2013

(Phys.org) —Newcastle University scientists have revealed the mechanism that causes a slime to form, making bacteria hard to shift and resistant to antibiotics.

Recommended for you

New tool identifies therapeutic proteins in a 'snap'

Aug 21, 2014

(Phys.org) —In human and bacterial cells, glycosylation – the chemical process of attaching complex sugar molecules to proteins – is as fundamental as it gets, affecting every biological mechanism from cell signaling ...

Treating pain by blocking the 'chili-pepper receptor'

Aug 20, 2014

Biting into a chili pepper causes a burning spiciness that is irresistible to some, but intolerable to others. Scientists exploring the chili pepper's effect are using their findings to develop a new drug ...

Moving single cells around—accurately and cheaply

Aug 19, 2014

Scientists at the Houston Methodist Research Institute have figured out how to pick up and transfer single cells using a pipette—a common laboratory tool that's been tweaked slightly. They describe this ...

The difficult question of Clostridium difficile

Aug 19, 2014

The bacterium Clostridium difficile causes antibiotic-related diarrhoea and is a growing problem in the hospital environment and elsewhere in the community. Understanding how the microbe colonises the hu ...

User comments : 0