Researchers discover how Bartonella causes deadly Oroya fever

Researchers discover how Bartonella causes deadly Oroya fever

The so-called “Oroya fever” is an extremely serious infectious disease, but is considered one of the so-called neglected tropical diseases. The infection has so far only occurred in high valleys in the South American Andes, especially in Peru, but also in Ecuador and Colombia. Therefore, it has received little attention in research and pharmaceutical development. Oroya fever is caused by the bacteriumBartonella bacilliformiswhich is transmitted through the bite of infected sand flies of the genusLutzomyia. The disease typically begins with high fever and massive destruction of red blood cells (erythrocytes), leading to severe hemolytic anemia. Without antibiotic treatment, Oroya fever is fatal in up to 90 percent of cases. Already 26 percent of pathogens are resistant to the standard antibiotic ciprofloxacin, which makes antibiotic treatment much more difficult.

LutzomyiaSand flies are currently only found in South America. However, due to global warming and increased travel, experts believe that the habitat of these sand flies could expand to other continents and even Europe.

An international research team led by Professor Volkhard Kempf from the University Medicine Frankfurt and the Goethe University has now generated and analyzed more than 1,700 genetic variants of the pathogen and identified two proteinsBartonellarequired for the destruction of red blood cells: a so-called porin, which enables the exchange of substances such as ions with the environment, and an enzyme called α/β hydrolase. Together, these two proteins are responsible for hemolysis. Structural analysis and targeted point mutations showed that the hemolytic activity ofBartonella bacilliformisdepends strictly on the enzymatic integrity of the α/β hydrolase.

Both proteins work together to destroy human erythrocytes, providing an explanation for the characteristic clinical presentation of Oroya fever. This makes the α/β hydrolase a suitable target protein for therapeutics.”

Dr. Alexander Poet, first author of the study

In laboratory experiments, the researchers also identified an inhibitor - a phospholipase inhibitor - that blocks the activity of α/β-hydrolase and can also prevent hemolysis of erythrocytes. “If we succeed in specifically eliminating the disease-causing effect of the bacterium in the human body in this way, we may have a therapy against which resistance is unlikely to develop,” says Töpfer.

"Oroya fever is a serious public health problem in Peru and South America, from which hundreds of people die every year without attracting attention from the rest of the world. The disease is caused by poverty and is one of the neglected tropical diseases that receive far too little attention," says Professor Volkhard Kempf, Director of the Institute for Medical Microbiology and Hospital Hygiene, which also houses the German Consultative LaboratoryBartonellaInfections (appointed by the Robert Koch Institute, Berlin). “We are all the more pleased that we have laid the foundation for the development of novel therapeutic approaches against Oroya fever and have thus made an important contribution to the fight against this fatally neglected tropical disease.”

Since the project's funding period has now expired, Kempf explains that efforts are being made to obtain further financial support to continue the research. "Now that we have elucidated the mechanisms of hemolysis, our next goal is to understand how the pathogen binds to erythrocytes, since the adhesion of pathogens to host cells is always the first step in any infection. We were able to elucidate the adhesion mechanisms of a related pathogen, the bacterium."Bartonella henselaea few years ago.”pical diseases.

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