Orthotopic Liver Transplantation: Is There a Risk for Listeria monocytogenes Infection?

Immunosuppression of any kind is a known risk factor for infection with Listeria monocytogenes (L. monocytogenes). Particularly, patients with impaired liver function are at increased risk of developing an aggravated course of infection with this bacterial pathogen (see Nolla-Salas et al.; 2002 and Cabellos et al.; 2008). It is a well-known pathogen in immunocompromised patients, but has only seldom been reported following orthotopic liver transplantation. Invasion of the central nervous system presenting as meningitis or meningoencephalitis and bacteremia are the principal clinical manifestations of listerial infections (see Brouwer et al.; 2006). We present an account of a case of a patient who developed L. monocytogenes meningitis during the early period after liver transplantation

Bartonella Adhesin A Mediates a Proangiogenic Host Cell Response

Bartonella henselae causes vasculoproliferative disorders in humans. We identified a nonfimbrial adhesin of B. henselae designated as Bartonella adhesin A (BadA). BadA is a 340-kD outer membrane protein encoded by the 9.3-kb badA gene. It has a modular structure and contains domains homologous to the Yersinia enterocolitica nonfimbrial adhesin (Yersinia adhesin A). Expression of BadA was restored in a BadA-deficient transposon mutant by complementation in trans. BadA mediates the binding of B. henselae to extracellular matrix proteins and to endothelial cells, possibly via β1 integrins, but prevents phagocytosis. Expression of BadA is crucial for activation of hypoxia-inducible factor 1 in host cells by B. henselae and secretion of proangiogenic cytokines (e.g., vascular endothelial growth factor). BadA is immunodominant in B. henselae–infected patients and rodents, indicating that it is expressed during Bartonella infections. Our results suggest that BadA, the largest characterized bacterial protein thus far, is a major pathogenicity factor of B. henselae with a potential role in the induction of vasculoproliferative disorders

Activation of Hypoxia-Inducible Factor-1 (HIF-1) and induction of proangiogenic cytokines after infection with Bartonella henselae

Bartonella spp. sind die einzigen bekannten bakteriellen Krankheitserreger, die beim Menschen vaskuloproliferative Krankheitsbilder wie z.B. Bazilläre Angiomatose und Peliosis hepatis hervorrufen können. Ziel der vorliegenden Arbeit war es, die von B. henselae induzierte proangiogenetische Wirtszellantwort zu analysieren. Im Rahmen dieser Arbeit konnte mittels Western blot gezeigt werden, dass die Infektion mit B. henselae in der Aktivierung von Hypoxia-Inducible Factor-1 (HIF-1), dem Schlüsseltranskriptionsfaktor der Angiogenese, resultiert. Im Verlauf der Infektion kommt es zur Synthese und Sekretion HIF-1-regulierter, angiogenetisch wirksamer Zytokine, wie z.B. vascular endothelial growth factor (VEGF), Adrenomedullin und insulin-like growth factor binding protein-3 (IGFBP-3). Interessanterweise ist die Aktivierung von HIF-1 in Wirtszellen nicht allein auf B. henselae beschränkt. Auch andere Bakterien wie z.B. Escherichia coli und Yersinia enterocolitica sind zur Aktivierung dieses Transkriptionsfaktors fähig. Allerdings resultiert einzig die Infektion mit B. henselae in der Sekretion der o.g. angiogenetisch wirksamen Zytokine. Als wesentlicher Pathogenitätsfaktor bei B. henselae-Infektionen fungiert Bartonella Adhäsin A (BadA), ein 340 kD großes äußeres Membranprotein, das für die Adhärenz von B. henselae an Endothelzellen und an Komponenten der extrazellulären Matrix eine entscheidende Rolle spielt. Die Expression von BadA ist entscheidend für die Aktivierung von HIF-1 sowie die nachfolgende Sekretion von proangiogenetischen Zytokinen in Wirtszellen durch Infektion mit B. henselae. Analog dazu führt eine BadA-defiziente Mutante - B. henselae BadA- - zu keiner Sekretion der o.g. vaskuloproliferativen Zytokine. Damit konnte in dieser Arbeit zum ersten Mal die Aktivierung von HIF-1 im Verlauf bakterieller Infektionen nachgewiesen werden. Weiterhin war es möglich, die wesentliche Rolle des Oberflächenmoleküls BadA an der Auslösung der proangiogenetischen Wirtszellantwort nach Infektion mit B. henselae zu belegen.Bartonella species are the only known bacterial pathogens causing vasculoproliferative disorders in humans, such as bacillary angiomatosis or peliosis hepatis. The thesis analysed the proangiogenic host cell response induced by infection with B. henselae. Activation of hypoxia-inducible factor-1 (HIF-1), the key transcription factor involved in angiogenesis, was detected in B. henselae-infected host cells in vitro by Western blotting. In the course of the infection HIF-regulated and vasculoproliferative cytokines are produced and secreted, for example vascular endothelial growth factor (VEGF), Adrenomedullin und insulin-like growth factor binding protein-3 (IGFBP-3). Interestingly the ability to activate HIF-1 in host cells is not restricted to B. henselae. Other bacteria such as Escherichia coli and Yersinia enterocolitica are able to activate this transcription factor, too. However, only the infection with B. henselae results in the secretion of the above mentioned angiogenic cytokines. A 340-kD outer membrane protein - Bartonella adhesin A (BadA) - is a major pathogenicity factor of B. henselae, it mediates the binding of B. henselae to extracellular matrix proteins and to endothelial cells. The expression of BadA is crucial for the activation of HIF-1 and the following secretion of proangiogenic cytokines in host cells after infection with B. henselae. Analogously a BadA-deficient mutant - B. henslae BadA- - is not able to induce the above mentioned vasculoproliferative cytokines. For the first time the data provide evidence that bacterial infections result in the activation of HIF-1. Furthermore it was possible to show the crucial role of the outer membrane protein BadA in the induction of the proangiogenic host cell response after infection with B. henselae

Leishmaniasis acquired by travellers to endemic regions in Europe – A EuroTravNet multi-centre study

BACKGROUND: Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. Clinical manifestations of leishmaniasis include cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). About 90% of cases occur in the tropics or subtropics but the disease is also endemic in the Mediterranean area. No systematic analysis on leishmaniasis in travellers visiting endemic areas in Europe is available. METHODS: Within the European travel medicine network EuroTravNet, we performed a retrospective analysis in travellers who acquired leishmaniasis within Europe diagnosed between 2000 and 2012. RESULTS: Forty cases of leishmaniasis (30 CL and 10 VL) were identified; the majority were acquired in Spain (n = 20, 50%), Malta and Italy (each n = 7, 18%). Median age was 48 years (range 1-79). Three of eight (37.5%) of the VL patients were on immunosuppressive therapy. The most frequent reason for travel was tourism (83%). Median duration of travel for patients with CL and VL was 2 weeks with ranges of 1-21 weeks in CL and 1-67 weeks in VL, respectively (P = 0.03). CONCLUSIONS: Health professionals should include leishmaniasis in the differential diagnosis in patients returning from southern Europe - including short-term travellers - with typical skin lesions or systemic alterations like fever, hepatosplenomegaly and pancytopenia