Infection studies: Antibodies prevent cell infection

Researchers from Goethe University, Frankfurt University Hospital, the Paul Ehrlich Federal Institute for Vaccines and Biomedical Research in Langen and the University of Oslo have used bacteria from the Bartonella hansel species to demonstrate, for the first time, that antibodies can block certain surface proteins of bacterial pathogens from entering host cells
.
These findings are important
for the development of new drugs against highly resistant infectious agents.

Infections, especially those of highly resistant pathogens, pose a significant threat
to human health.
It is dangerous
when the pathogen manages to colonize the organism and subsequently cause a serious infection.
The first step in this infection is always the pathogen attaching to the surface
of the host cell.
From here, the infection spreads, for example, leading to infection
of deeper layers of tissue and organs.

A team of scientists around Professor Volkhard Kempf from the Institute of Microbiology and Hospital Hygiene at the University Hospital Frankfurt has now succeeded in blocking the adhesion mechanism of bacteria and thus preventing infection
of host cells.
To do this, the researchers examined Bartonella henselae, which usually causes scratch disease in cats
.
The disease is transmitted by cats and mainly affects young children, with symptoms including swollen and hardening of the lymph nodes around the site of infection, usually after
a scratch or bite caused by an infected cat.

Bartonella bacteria infect so-called vascular endothelial cells
.
Through their surface protein, Bartonella adhesion A (BadA), they attach themselves to a protein called the "extracellular matrix" (fibronectin), a network
of protein fibers located on top of endothelial cells.

To determine which parts of the BadA protein are important during bacterial adhesion, the researchers provided Bartonella bacteria with various transgenic BadA variants and then analyzed the extent to which these variants were still able to
bind fibronectin.
Once it was clear which BadA fragments were responsible for binding, the team generated antibodies against them and, using cell culture experiments, showed for the first time that this antibody could prevent infection
with this bacterium.

Professor Volkhard Kempf explains: "Bartonella hensel is not a very dangerous pathogen and in most cases cat scratches do not require any specific medical treatment
.
However, for us, Bartonella hansel is a very important model organism for more dangerous pathogens than pathogens such as Acinetobacter baumannii, a serious pathogen that often causes wound infection or pneumonia and often shows resistance to several antibiotics of last resort
.
The BadA protein of Bartonella hansel belongs to the so-called "trimeric autotransporter", which is also responsible for the adhesion
of Acinetobacter and some other pathogens to human cells.
Therefore, drug-induced blockade of these adhesin proteins is a promising novel and future method to combat dangerous bacterial infections
.
”

Journal Reference:

1. Arno Thibau, Diana J.
   Vaca, Marlene Bagowski, Katharina Hipp, Daniela Bender, Wibke Ballhorn, Dirk Linke, Volkhard A.
   J.
   Kempf.
   Adhesion of Bartonella henselae to Fibronectin Is Mediated via Repetitive Motifs Present in the Stalk of            Bartonella            Adhesin A.
   Microbiology Spectrum, 2022; DOI: 10.
   1128/spectrum.
   02117-22