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Oroya fever is a serious infectious disease and belongs to the group of so-called neglected tropical diseases. It is transmitted by infected Lutzomyia sandflies, which are currently only found in South America. However, as a result of climate change and increasing travel freqency, experts expect that the distribution of these sandflies could expand to other continents and even to Europe in the future. The infection currently occurs exclusively in high-altitude valleys of the South American Andes, primarily in Peru, but also in Ecuador and Colombia. Consequently, the disease has received little attention from research and drug development. The illness usually begins with high fever and massive destruction of red blood cells (erythrocytes), resulting in hemolytic anemia. Without antibiotic treatment, Oroya fever is fatal in up to 90 percent of cases. Already 26 percent of the pathogens are resistant to the standard antibiotic ciprofloxacin, which makes antibiotic treatment significantly more difficult.

An international research team led by Prof. Volkhard Kempf from University Hospital Frankfurt and Goethe University has now produced and analyzed more than 1,700 genetic variants of the pathogen, identifying two proteins that Bartonella requires to destroy red blood cells: a so-called porin, which enables for example the exchange of ions with the environment and an enzyme called α/β-hydrolase, both of which together are responsible for hemolysis. Structural analyses and targeted point mutations showed that the hemolytic activity of Bartonella bacilliformis depends strictly on the enzymatic integrity of α/β-hydrolase. […]

In laboratory experiments, researchers have now identified an inhibitor, a phospholipase inhibitor, that blocks the activity of α/β-hydrolase and can also prevent the hemolysis of erythrocytes. "If it were possible to selectively eliminate the pathogenic effect of the bacterium in the human body in this way, we might have a therapy against which resistances could hardly develop," says Dr. Alexander A. Dichter, lead author of the recently published paper.

"Oroya fever is a serious health problem in Peru and South America, claiming hundreds of lives every year, yet it goes largely unnoticed by the rest of the world. […] We are therefore all the more pleased to have laid the foundation for the development of novel therapies against Oroya fever, thus making an important contribution to the fight against this neglected tropical disease." […] "Following the end of funding for the LOEWE Center DRUID, we are now seeking financing to continue the research," said Kempf. "Having elucidated the hemolysis mechanism, our next goal is to understand how the pathogen binds to erythrocytes, since the adherence of pathogens to host cells is always the first step in an infection. We were able to explain the adherence mechanisms of a related pathogen, the bacterium Bartonella henselae, several years ago."