Persistent bacteria How staphylococci enter the organism

Common pathogens: how staphylococci accumulate in 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 controlling such bacteria.

Laws of physics

Bacteria have developed sophisticated strategies to establish and multiply in their hosts. The role played by the laws of physics is shown by a study published in the journal "Science". Using the example of staphylococci, the research team has investigated the extraordinary mechanical persistence of bacteria in binding proteins to the target molecules of their host. The scientists have succeeded in decoding the physical mechanism by which the pathogen attaches to its target molecule. In addition, they represent the process in unprecedented detail accuracy.

Researchers were able to decipher the physical mechanism by which a common pathogen binds to its target in the human body. The new findings could contribute to the development of novel therapies. (Image: Alexander Raths / fotolia.com)

Staphylococci are the cause of many infectious diseases

"Staphylococci are the cause of many infectious diseases in humans and animals. They can cause both food-borne poisoning and 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 experts are particularly concerned about the 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 the Ludwig-Maximilians-University (LMU) Munich in collaboration with researchers from the University of Illinois (USA) have the physical forces between a pathogen adhesion protein and its human target molecule Measured at the single molecule in vitro by means of scanning force microscopy.

In addition, they have calculated the interaction of all atoms involved in a particularly powerful supercomputer, it says in a statement.

"This paradigm shift provides insights that were not possible before," says Gaub. For example, on the supercomputer Blue Waters in Illinois, one of the world's strongest computers with 900,000 processors, parallel molecular dynamics simulations were run in order to decode the complex interplay.

The force with which the pathogen binds to its target molecule surprised the researchers: "The mechanical binding strength of a single receptor-ligand complex reached a force of more than two nanoneewtons. This is an extraordinary stability comparable to the strength of covalent bonds between atoms, the strongest molecular forces we know, "explains Gaub.

Bacterium uses an unusual mechanism

The study shows that the adhesion protein of the bacterium, thanks to its geometry, embeds the target molecule in a hydrogen-bonding network that is dominated by the peptide backbone rather than by its side chains.

Under the force of innumerable small local interactions, these bonds are stiffened into 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," said Gaub.

Since the mechanism is focused on the peptide backbone, which is similar for each protein, the high stability can be achieved for a broad spectrum of target peptides.

Thus, the extreme physical strength of the system is largely independent of the sequence and biochemical properties of the target.

Foundations for the development of new therapies

"Diseased bacteria adhere to the target molecules of their hosts with exceptional mechanical persistence," explains Gaub.

"Understanding the physical mechanisms that underlie this stubborn adhesion at the molecular level is critical to fighting such invaders," said the expert.

Thus, the study laid the foundations for the development of novel therapies for infections with staphylococci. (Ad)