The unnoticed bacterium
In contrast to the USA, human granulocytic anaplasmosis (HGA) infection rarely occurs in Germany. Dr. Friederike von Loewenich and her team at the Freiburg Institute for Medical Microbiology and Hygiene are investigating the reason for this discrepancy. Could it be that the German strains of the Anaplasma phagocytophilum bacteria are less dangerous than their American relatives? Or is there some other reason?
This is what an Anaplasma phagocytophilum infected granulocyte looks like. The pathogens form membrane-enclosed agglomerates (the two light lilac structures below the dark lilac nucleus). (Figure: Dr. Friederike von Loewenich)
In the 1930s, Anaplasma phagocytophilum bacteria were discovered in sheep and cattle in Europe for the first time. Animals as well as humans can be infected with these bacteria through ticks. The bacteria enter the bloodstream and attack neutrophil granulocytes, a type of white blood cells in humans that are part of the immune system, in which the bacteria form membrane-enclosed agglomerates and proliferate.
Anaplasmosis weakens the immune system and leads to flu-like symptoms such as weakness, fever, aching muscles and headaches. Infection may occasionally lead to organ failure and be life-threatening or even fatal. Since 1994, approximately 3,000 people have been infected with Anaplasma phagocytophilum in the USA. “In contrast to the USA, only a few people have been diagnosed with HGA in Germany. The first case occurred in 1997,” said Dr. von Loewenich, head of a group of researchers at the Institute for Medical Microbiology and Hygiene at the University Hospital of Freiburg. “This seems rather strange, at least at first sight,” said von Loewenich.
Are the European strains less dangerous?According to von Loewenich, this difference may have two reasons: Either the German strains are less pathogenic than the American ones and therefore lead to fewer infections, or they are as pathogenic as their American relatives and lead to just as many infections.
In the latter case, it must then be assumed that European doctors often do not diagnose the disease. “Incorrect diagnoses might well be possible, especially in the case of Anaplasma phagocytophilum,” said von Loewenich who has been dealing with the bacteria for eight years. “It is difficult to identify the bacteria in routine tests because they cannot be grown on common bacterial media. The disease can only be detected through special blood tests, which are, however not routine in patients complaining of flu-like symptoms.”
Specific antibodies of the affected patient recognise bacterial structures in cells that are infected with Anaplasma phagocytophilum. The bound patient antibodies are visualised under the fluorescence microscope by secondary antibodies that are coupled to fluorescent dyes. (Picture: Dr. Friederike von Loewenich)
Dr. von Loewenich and her team investigated whether their second hypothesis explained the low anaplasmosis incidence in Europe. They used molecular genetics methods to find differences between the American and a total of 181 pathogenic European strains. For example, they looked at the DNA sequence of the Anaplasma-specific gene ank. The result showed that the genes of the American and European strains are very similar, which should make the European strains as pathogenic as their American relatives. “We therefore presume that it is difficult to diagnose the disease, which is why many anaplasmosis infections go undetected.”
Unusual control mechanisms
Polymerase chain reaction (PCR) and gel electrophoresis are used to identify specific genes of the bacteria. (Photo: Dr. Friederike von Loewenich)
Anaplasma bacteria are very special, also in terms of detectability. It seems as if the immune system controls the pathogens differently from other pathogens. The Anaplasma cell wall lacks typical recognition features such as peptidoglycans or lipopolysaccharides (LPS). LPS are usually bound by structures on the cell membranes of the immune system cells and initiate complex signalling cascades that in turn induce a defence programme in the cell. However, Dr. von Loewenich and her team experimented on mice and were able to show that the typical MyD88 surface structure is not required for Anaplasma bacteria to be recognised. Far more important are T-helper cells on the surface of which the CD4 molecule can be found; the elimination of pathogens is impossible without these cells.
“In future projects, we hope to gain a better understanding of the interaction of this T-cell type and the infected neutrophil granulocytes,” said von Loewenich. “How do T-cells succeed in eliminating infected granulocytes?” In addition, the Freiburg researchers have plans to examine how the human immune system recognises these bacteria, since the usual receptors do not seem to be an important factor. Being difficult to detect, the bacteria might therefore provide the field of immunology with completely new discoveries and become more important, at least among researchers.
mn – 11 August 2008
© BIOPRO Baden-Württemberg GmbH
Further information:
Dr. med. Friederike von Loewenich
Institute for Medical Microbiology and Hygiene
Hermann-Herder-Str. 11
79104 Freiburg
Tel.: +49-761/203-5359
Fax: +49-761/203-6651
E-mail:
friederike.loewenich@uniklinik-freiburg.de