A unique biofilm in human deep mycoses: fungal amyloid is bound by host serum amyloid P component

Abstract

Background/ObjectivesWe have demonstrated the presence of Candida cell surface amyloids that are important in aggregation of fungi and adherence to tissue. Fungal amyloid was present in invasive human candidal infections and host serum amyloid P component (SAP) bound to the fungal amyloid. SAP is a protease-resistant glycoprotein that binds avidly to amyloid and interferes with host defence, especially against bacterial pathogens for which neutrophils are important. In this study, we investigated whether biofilm of fungal amyloid and SAP was a feature of other disseminated fungal infections.MethodsTissue specimens from 15 autopsies were systematically evaluated with multiple histochemical stains including thioflavin T and Congo red (dyes that stain amyloid), as well as antibody to SAP. We studied specimens with disseminated aspergillosis, mucormycosis and coccidioidomycosis. The structure of the lesions, host inflammatory cells and the presence of fungal amyloid and SAP were determined.ResultsThe structure of the lesions was characteristic in aspergillosis (‘starburst’) and mucormycosis (closely apposed bundles of hyphae). Host inflammatory cells were absent or few in number within these lesions. In Coccidioides lesions, host inflammation was sparse as well. Fungal amyloid was a prominent feature of all lesions along with abundant SAP bound to hyphae and spherules. Fungal amyloid and SAP perhaps contributed to persistence in caseous necrosis lesions. SAP also bound to Aspergillus and Mucorales amyloid in vitro.ConclusionsA biofilm including amyloid and SAP is present in invasive fungal infections. This biofilm may dampen host defence leading to the characteristic sparse inflammatory reaction found in these infections.

Serum Amyloid P Component and Systemic Fungal Infection: Does It Protect the Host or Is It a Trojan Horse?

“…More recent work extends our findings with fungal amyloid to include other pathogenic fungi that bind SAP [ 16 ]. We studied autopsy tissue from individuals with invasive aspergillosis, mucormycosis, and coccidioidomycosis.…”

The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins

“…Noticeably, high levels of CRP have been reported in IA patients [106,107], and this pentraxin has been described to recognize yet unknown components of the hyphal cell wall of A. fumigatus [108] and promote phagocytosis of germinating (more than dormant) conidia by human neutrophils in vitro [109]. Also, SAP has been shown to localize in areas of hyphal dissemination in the lung parenchyma of IPA patients [110] and attenuate some traits (i.e., airway resistance to methacholine, inflammation, and tissue remodeling) of the chronic allergic airway disease in A. fumigatus-sensitized mice, possibly via modulation of the M2 polarization of macrophages [111]. This information notwithstanding, if and how the short pentraxins participate in the pathogenesis of aspergillosis in vivo is currently unclear.…”

“…Despite of their involvement in a number of infectious diseases [104], very few clinical records are available to indicate or suggest an etiopathogenic role of the short pentraxins in human aspergillosis. In this regard, CRP has been proposed as a prognostic factor for survival in patients with acute invasive fungal rhinosinusitis [165], and SAP has been observed in human specimens with disseminated aspergillosis in areas of biofilm amyloid accumulation [110], which potentially suggests a role for this protein in the adhesion of A. fumigatus (mostly hyphae) to the lung tissue. As opposed to the short pentraxins, common polymorphisms in the PTX3 gene have been proposed as critical risk factors for IPA in patients undergoing hematopoietic stem-cell transplantation (HSCT) [166].…”

Rational Design of Amyloid‐Like Fibrillary Structures for Tailoring Food Protein Techno‐Functionality and Their Potential Health Implications

“…In addition, more recent work has identified multiple cases of amyloid fibers in bacteria, fungi, insects, invertebrates, and humans that serve several important functional roles (Barlow et al., ; Fowler, Koulov, Balch, & Kelly, ; Gebbink et al., ). Examples of such functional amyloids are those involved in biofilms formed by bacteria (for example, curli and chaplins proteins secreted by E.coli and Streptomycetes , respectively; Garcia‐Sherman, Lundberg, Sobonya, Lipke, & Klotz, ; Gebbink et al., ), fungal adherence (for example, hydrophobins; Garcia‐Sherman et al., ), barnacle attachment to the marine surface (Nakano & Kamino, ), and the formation of the amyloid coat of mammalian oocytes by the zona pellucida protein (Egge, Muthusubramanian, & Cornwall, ). Another example is that the amyloid form of the human premelanosome protein protects melanocytes from melanin polymerization toxicity (Watt, van Niel, Raposo, & Marks, ).…”