Widespread pathogen: How staphylococci attach themselves to the body
German researchers have deciphered the physical mechanism by which a common pathogen binds to its target molecule in the human body. The new findings are crucial for the control of such bacteria.
Laws of physics
Bacteria have developed sophisticated strategies to establish and multiply in their hosts. What role the laws of physics also play is shown in a study that has now been published in the scientific journal Science. Using the example of staphylococci, the research team investigated the extraordinary mechanical persistence with which bacteria bind to the target molecules of their host using proteins. The scientists have succeeded in deciphering the physical mechanism by which the pathogen attaches to its target molecule. In addition, they represent the process in unprecedented level of detail.
Staphylococci are the cause of many infectious diseases
“Staphylococci are the cause of many infectious diseases in humans and animals. They can lead to food-borne poisoning as well as to infectious diseases, ”explains the Federal Institute for Risk Assessment (BfR) on its website.
"They often cause purulent wound infections and other purulent infections in humans." For example, the bacteria are often responsible for inflammation in the nose.
Staphylococci can also lead to the so-called toxic shock syndrome.
Health professionals are particularly concerned about multidrug-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), which are often resistant to antibiotics.
Insights that were not possible before
As part of the current study, Lukas Milles and Professor Hermann Gaub from the Faculty of Physics at Ludwig Maximilians University (LMU) Munich, in collaboration with researchers from the University of Illinois (USA), have the physical forces between an adhesion protein of a pathogen and its human target molecule measured on a single molecule in vitro using atomic force microscopy.
In addition, they have calculated the interaction of all atoms involved on a particularly powerful supercomputer, according to a message.
"This paradigm shift opens up insights that were previously not possible," says Gaub. For example, parallel molecular dynamics simulations were run on the supercomputer Blue Waters in Illinois, one of the world's most powerful computers with 900,000 processors, in order to decode the complex interaction.
The researchers were surprised by the force with which the pathogen binds to its target molecule: “The mechanical bond strength of a single receptor-ligand complex reached a force of over two nanonewtons. This is an extraordinary stability comparable to the strength of covalent bonds between atoms, the strongest molecular forces that we are familiar with, ”explains Gaub.
Bacteria uses an unusual mechanism
The study shows that the bacteria's adhesive protein, thanks to its geometry, embeds the target molecule in a hydrogen-bond network that is dominated by the peptide backbone rather than its side chains.
Under the force of countless small local interactions, these bonds stiffen into a cooperative shear geometry, as the underlying physical principle is called.
"This geometry can withstand extreme forces because all bonds would have to be broken in parallel to separate the target," says Milles.
A simplified analogy is two Velcro strips that are difficult to separate when pulled from opposite ends.
"The bacterium uses an unusual mechanism, but it is very sophisticated and gives it decisive advantages," says Gaub.
Because the mechanism is focused on the peptide backbone, which is similar for each protein, high stability can be achieved for a wide range of target peptides.
As a result, the extreme physical strength of the system is largely independent of the sequence and the biochemical properties of the target.
Basis for the development of new therapies
"Pathogenic bacteria adhere to the target molecules of their hosts with exceptional mechanical persistence," explains Gaub.
"Understanding the physical mechanisms underlying this stubborn adhesion at the molecular level is critical to fighting such intruders," said the expert.
The study thus laid the foundations for the development of new therapies for infections with staphylococci. (ad)