Bacteria Adhesion Discovery Moves Team Closer to New Antibiotics

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Adhesion of Bartonella henselae (blue) to human blood vessel cells (red). The bacterium's adhesion to the host cells could be blocked with the help of what are known as “anti-ligands”. Credit: DOI: 10.3390/diagnostics11071259

Researchers from University Hospital Frankfurt and Goethe University Frankfurt have unraveled how bacteria adhere to host cells and thus taken the first step toward developing a new class of antibiotics.

The adhesion of bacteria to host cells is always the first and one of the decisive steps in the development of infectious diseases. The purpose of this adhesion by infectious pathogens is first to colonize the host organism, and then trigger an infection, which in the worst case can end fatally. Precise understanding of the bacteria's adhesion to host cells is a key to finding therapeutic alternatives that block this critical interaction in the earliest possible stage of an infection.

In collaboration with other researchers, scientists from University Hospital Frankfurt and Goethe University Frankfurt have now explained the exact bacterial adhesion mechanism using the human-pathogenic bacterium Bartonella henselaeThis pathogen causes "cat-scratch disease," a disease transmitted from animals to humans. 

In a project led by Volkhard Kempf, the bacterial adhesion mechanism was deciphered with the help of a combination of in-vitro adhesion tests and high-throughput proteomics. 

The scientists have shed light on a key mechanism: the bacterial adhesion to the host cells can be traced back to the interaction of a certain class of adhesins—called "trimeric autotransporter adhesins"—with fibronectin, a protein often found in human tissue. Adhesins are components on the surface of bacteria which enable the pathogen to adhere to the host's biological structures. Homologues of the adhesin identified here as critical are also present in many other human-pathogenic bacteria, such as the multi-resistant Acinetobacter baumannii, which the World Health Organization (WHO) has classified as the top priority for research into new antibiotics.

State-of-the-art protein analytics were used to visualize the exact points of interaction between the proteins. In addition, it was possible to show that experimental blocking of these processes almost entirely prevents bacterial adhesion. Therapeutic approaches that aim to prevent bacterial adhesion in this way could represent a promising alternative treatment as a new class of antibiotics (known as “anti-ligands”) in the constantly growing domain of multi-resistant bacteria.

Republished courtesy of Goethe University Frankfurt.

 

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