Mucormycosis

Mucormycosis is a group of mould infections caused by fungi in the order Murocales.[1][2]

Agents of mucormycosis are ubiquitous in soil and can be found on decaying organic matter such as food, hay, and vegetation.[2] Carbohydrate substrates promote rapid growth of hyphae and asexual sporangiospores to help efficient dissemination into the environment. The most common mode of acquiring infection is through inhalation, although infection can also be acquired through cutaneous and subcutaneous inoculation.

The characteristic features of the agents of mucormycosis are broad hyphae.[26]

In culture: non-septate hyphae and sporangia containing sporangiospores supported by sporangiophores.
In tissue: aseptate to minimally septate hyphae branching at 90°.

Inhalation of spores is the most common mode of entry. The spores then germinate to produce hyphae, which invade blood vessels, causing thrombosis and subsequent tissue necrosis. Invasion of the vessels also promotes dissemination of the fungus to other organs. Normal mononuclear and polymorphonuclear phagocytes are essential to kill Mucorales by generating oxidative metabolites and cationic peptide defensins.[27] Macrophages inhibit spore germination and neutrophils damage hyphae.

Various factors increase the risk of acquiring mucormycosis by impairing either quantity of neutrophils, as in chemotherapy-induced neutropenia, or quality of neutrophils, as with corticosteroids and acidosis.

Hyperglycaemia and acidosis interfere with the oxidative and non-oxidative ability of the phagocytes to move towards and kill the organisms. Macrophage function to prevent germination of spores in vitro and in vivo is affected by corticosteroids in animal models. The exact mechanisms for the above actions are unknown.[3] When applicable, reversal of acidosis in addition to early recognition, with appropriate treatment, results in better outcomes.

Experimental evidence suggests the role of iron in the pathogenesis of mucormycosis. Desferrioxamine, an iron chelator, a siderophore, forms a complex with iron, which stimulates growth of Rhizopus in vitro and pathogenicity in vivo.[28]

Pre-germinated spores of R oryzae can adhere to the sub-endothelial matrix. These spores can cause damage after phagocytosis by the endothelial cells. Spore viability is not required to cause cell damage, implying that cidal antifungal agents do not affect the clinical course in established disease.[3]

Taxonomic classification of clinically significant agents of mucormycosis

Mucormycosis was previously known as zygomycosis, from the phylum Zygomycota. However, molecular studies have led to the taxonomic reclassification of a number of fungal groups. Phylogenetic analysis led to the reclassification of the phylum Zygomycota, which was replaced by two distinct phyla: Zoopagomycota and Mucoromycota. Mucoromycota is further divided into three subphyla: Glomeromycotina, Mortierellomycotina, and Mucoromycotina, with the latter encompassing the orders Mucorales, Umbelopsidales, and Endogenales.[1] The Entomophthoromycetes, now classified under Zoopagomycota, are not included in mucormycosis, but are included in the former term zygomycosis.[5] Infections by Mucorales are called mucormycosis, while those by Entomophthorales are termed entomophthoromycosis.[1][6] The taxonomic classification of these fungi is an active area of research, a full review of which is out of the scope of this topic.

Order: Mucorales

Organisms in this group can cause fatal infections in the immunocompromised host.
Mucorales comprises 55 genera and 261 species, with 11 genera and 39 species known to cause human infections. Clinically significant genera include:[1][6]
- Actinomucor (species: A elegans)
- Apophysomyces (species: A mexicanus; A ossiformis; A trapeziformis; A variabilis)
- Cokeromyces (species: C recurvatus)
- Cunninghamella (species: C arunalokei; C bertholletiae; C blakesleeana; C echinulata; C elegans)
- Lichtheimia (species: L corymbifera; L ornata; L ramosa)
- Mucor (species: M amphibiorum; M circinelloides; M griseocyanus; M indicus; M irregularis; M janssenii; M lusitanicus; M plumbeus; M racemosus; M ramosissimus; M variicolumellatus; M velutinosus)
- Rhizomucor (species: R miehei; R pusillus)
- Rhizopus (species: R arrhizus [including var. arrhizus and var. delemar]; R homothallicus; R microsporus; R schipperae)
- Saksenaea (species: S erythrospora; S loutrophoriformis; S trapezispora; S vasiformis)
- Syncephalastrum (species: S racemosum)
- Thamnostylum (species: T lucknowense)

Order: Entomophthorales

Infections from these organisms would not be considered mucormycosis, but were included in the former term zygomycosis.
Organisms in this group usually cause indolent skin, subcutaneous, nasal, and sinus infections in immunocompetent people in tropical and subtropical regions.
Only two genera are implicated in human infection, including:[5]
- Conidiobolus (species: C coronatus; C incongruus;C lamprauges)
- Basidiobolus (species: B ranarum).

Pathophysiology

Classification

Taxonomic classification of clinically significant agents of mucormycosis