Pathogenicity patterns of mucormycosis: epidemiology, interaction with immune cells and virulence factors

Abstract

Fungi of the basal lineage order Mucorales are able to cause infections in animals and humans. Mucormycosis is a well-known, life-threatening disease especially in patients with a compromised immune system. The rate of mortality and morbidity caused by mucormycosis has increased rapidly during the last decades, especially in developing countries. The systematic, phylogenetic, and epidemiological distributions of mucoralean fungi are addressed in relation to infection in immunocompromised patients. The review highlights the current achievements in (i) diagnostics and management of mucormycosis, (ii) the study of the interaction of Mucorales with cells of the innate immune system, (iii) the assessment of the virulence of Mucorales in vertebrate and invertebrate infection models, and (iv) the determination of virulence factors that are key players in the infection process, for example, high-affinity iron permease (FTR1), spore coat protein (CotH), alkaline Rhizopus protease enzyme (ARP), ADP-ribosylation factor (ARF), dihydrolipoyl dehydrogenase, calcineurin (CaN), serine and aspartate proteases (SAPs). The present mini-review attempts to increase the awareness of these difficult-to-manage fungal infections and to encourage research in the detection of ligands and receptors as potential diagnostic parameters and drug targets.

How could hypoglycemia-inducing glycogen storage disease lead to hyperglycemia-induced mucormycosis?

“…These spores are ubiquitous in the air all around the world. 2 Infection is not with the inhaled resting spore forms, but with hyphal forms of the mucoralean fungi. One virulence factor of the mucoralean fungi is rapid germination from spores to hyphae.…”

“…Rhizopus species inhibit phagosome maturation in macrophages by the melanin on the spore surface. 2 Rhizopus species also resist being damaged or killed by decreasing the oxidative burst of phagocytes, which is another virulence factor. 3 Spore coat protein CotH of mucoralean fungi binds to glucose-regulated protein 78 (GRP78) on endothelial cells, promoting angioinvasion, which results in thrombosis and tissue necrosis, yet another virulence factor.…”

Tornadic shear stress induces a transient, calcineurin-dependent hyper-virulent phenotype in Mucorales molds

“…In line with these observations, RNA sequencing analysis of R. arrhizus revealed a very low number of significantly differentially expressed transcripts upon TSC. Specifically, no genes that are known or suspected to be immediately linked with Mucoralean virulence such as epithelial invasins, toxins, or proteins related to iron metabolism (38) were differentially expressed after TSC. While the identification of novel virulence factors and interpretation of the few differentially regulated transcripts is complicated by the sparse annotation of the Rhizopus genome and very limited experimental characterization of Mucoralean gene functions, the overall minimal transcriptional changes and rapid decay of hyper-virulence suggest a role of post-translational events that would have not been captured by our sequencing approach.…”

The geographical region of origin determines the phagocytic vulnerability of Lichtheimia strains

“…During the last decades Lichtheimia distributed from the plant/soil‐associated forms to the clinical environment (de Hoog et al ., ) and became an emerging causative agent of invasive mucormycoses (Hassan and Voigt, ). Additionally, Lichtheimia species show a wide geographical distribution across all continents; with species being isolated from either the environment or from human specimens (Hassan and Voigt, ). Moreover, Lichtheimia species cause severe diseases to a large variety of animals including cattle, horse and stork (Schwartze and Jacobsen, ).…”