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A probable cause of paradoxical thrombosis in zygomycosis

R Rüchel1, C Elsner, A Spreer

  • 1Department of Bacteriology, University Hospital, Göttingen, Germany. rrueche@gwdg.de

Mycoses
|June 11, 2004
PubMed

Insights

Invasive zygomycoses, or mucormycoses, are rare, deadly fungal infections. This study suggests fungal proteinase and patient leukocyte elastase jointly cause blood clotting in these infections.

Area of Science:

  • Mycology
  • Hematology
  • Infectious Diseases

Background:

  • Invasive zygomycoses (mucormycoses) are rare but severe, often fatal fungal infections.
  • These infections are frequently seen in diabetics and individuals with iron overload (siderophilia).
  • A common complication is thrombosis leading to tissue death (necrosis), often originating as rhinocerebral sinusitis.

Purpose of the Study:

  • To investigate the mechanisms behind the blood clotting associated with invasive zygomycosis.
  • To identify the specific factors contributing to thrombosis in a patient infected with Rhizopus microsporus.

Main Methods:

  • Utilized a clinical isolate of Rhizopus microsporus and serum from a human survivor.
  • Performed in vitro experiments to analyze the interaction of fungal and host factors on blood coagulation.

Main Results:

  • Identified a fungal extracellular serine proteinase and patient leukocyte elastase as key players in initiating coagulation.
  • Demonstrated that the fungal proteinase partially hydrolyzes fibrinogen.
  • Showed that elastase activates coagulation factor XIII (fibrin stabilizing factor).
  • Confirmed that both proteinases, present at the infection site, synergistically induce fibrinogen clotting in vitro.

Conclusions:

  • Blood clotting in invasive zygomycosis is likely a bimodal process involving both fungal and host-derived proteases.
  • Fungal serine proteinase and leukocyte elastase work together to promote thrombosis and necrosis in these infections.
  • Understanding this dual mechanism may offer targets for therapeutic interventions against zygomycosis-associated coagulopathy.

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