# A potential histoplasmosis pathogenesis mechanism mediated by a lectin of Histoplasma capsulatum with affinity to β-galactose, favoring intravascular hemagglutination

## TL;DR

This paper explores how a lectin from the fungus Histoplasma capsulatum may cause dangerous blood clots in severe histoplasmosis patients.

## Contribution

The study identifies a conserved β-galactose-binding lectin in H. capsulatum that may mediate intravascular hemagglutination and worsen disease outcomes.

## Key findings

- H. capsulatum yeasts from multiple strains cause human erythrocyte hemagglutination inhibited by β-galactose.
- A β-galactose-binding lectin was partially purified and shown to be conserved across genetically distinct isolates.
- Histopathological evidence supports erythrocyte adherence by H. capsulatum, suggesting intravascular hemagglutination.

## Abstract

Ascomycetes belonging to the Histoplasma capsulatum species complex can cause severe manifestations in patients with disseminated histoplasmosis. Based on data from hemagglutination assays and histopathological findings related to H. capsulatum, we investigated their potential role in the disseminated intravascular hemagglutination events. Human erythrocyte hemagglutination was produced with H. capsulatum yeasts of 10 isolates/strains, belonging to different phylogenetic species and lineages. Hemagglutination assays were inhibited by pre-incubating their yeasts with β-galactose, ratifying previously published data for a unique H. capsulatum clinical strain. This lectin was partially purified through affinity chromatography using erythrocyte stroma, and its hemagglutinating activity was confirmed. Results underlined the consistent involvement of a β-galactose-binding lectin of H. capsulatum yeasts in hemagglutination assays by using genetically distinct H. capsulatum species, which support its conserved origin. Serendipitous findings in histopathological sections of human and bat tissues supported that H. capsulatum yeasts adhered to erythrocytes, consistent with intravascular hemagglutination. Hence, in hosts with disseminated histoplasmosis and sepsis, we hypothesized that this H. capsulatum lectin may favor an intravascular hemagglutination, which could occur concomitantly with a procoagulant state, aggravating hypoxia and leading to disseminated intravascular coagulation, a lethal complication.

Histoplasmosis, caused by Histoplasma capsulatum complex, is a respiratory-systemic mycosis prevalent in the Americas. This disease can display life-threatening acute pulmonary and disseminated clinical forms. Here, we hypothesized that the hemagglutinating activity mediated by the β-galactose-binding lectin present on yeasts of genetically distinct H. capsulatum isolates/strains could be involved in the fatal complications of septic patients, such as disseminated intravascular coagulation.