Invasive Pulmonary Aspergillosis Due to Aspergillus awamori: Role of Calcium Oxalate Crystal Precipitation Mimicking Mucormycosis

Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.

“…Oxalic acid and oxalate crystals are thought to cause host tissue damage (including in pulmonary blood vessels), as well as tissue injury via iron-dependent generation of free radicals ( 157 , 163 ). A mechanical role of CaOx crystals was recently reported by Yi et al ( 164 ) in a case of pulmonary angioinvasive aspergillosis in a Burkitt’s lymphoma patient with severe neutropenia, with pathophysiological examinations showing the presence of CaOx crystals around and within the walls of blood vessel. Aside from mechanical damage to the host tissues, the formation of CaOx could also have a dramatic effect on cell physiology.…”

“…This may be necessary for their capacity to colonize or cause infection, via the secretion of oxalic acid or other low molecular weight organic acids. Several studies have reported the presence of CaOx crystals in the case of pulmonary aspergillosis ( 154 – 164 ), and the detection of CaOx crystals has been proposed as an easy tool for differential diagnosis ( 162 ). In most of the reported cases, oxalate deposition was associated with A. niger infection, but some reports also include infection caused by A. flavus or A. fumigatus ( 159 ).…”

Biocontrol ofAspergillus nigerin 3D-lung cell tissues by oxalotrophic bacteria

“…A recent case report of invasive pulmonary aspergillosis in a 69-year old man with lymphoma and pneumonia indicated the presence of calcium oxalate crystals around blood vessels and within the blood vessel walls. This suggests a potential mechanical role of oxalate crystals in the angioinvasion of Aspergillus (Yi et al, 2019). However, a link between oxalic acid production and pathogenicity has not yet been made in fungi from this genus or in any other fungal human pathogen; despite having been widely acknowledged in the case of fungal plant pathogens, where pH manipulation by the secretion of oxalic acid plays a direct role in pathogenesis (Dutton and Evans, 1996; Lehner et al, 2008; Palmieri et al, 2019).…”

“…nutritional plasticity, reproductive success, and tolerance to environmental stressors), the ability to manipulate pH via the secretion of low molecular weight organic acids, and in particular, oxalic acid, has been largely ignored in the context of human pathogenesis. Several clinical reports have shown the presence of calcium oxalate crystals in pulmonary aspergillosis in animals and humans (Kurrein et al, 1975; Maeno et al, 2015; Muntz, 1999; Oda et al, 2013; Payne et al, 2017; Yi et al, 2019). Oxalic acid and oxalate crystals are thought to directly cause damage to the host tissues (including pulmonary blood vessels), and to generate free radicals which can harm cells indirectly (Payne et al, 2017).…”