Hyphae of M. irregularis are characterized as hairy, whitish, and pale-yellow, sporangiophores are hyaline, up to 2 mm high, 10-20 um wide, sympodially and monopodially branched arising from abundant branched hyphae, branches all ending in a sporangium Sporangia (sub)spherical, up to 100 μm diameter; membrane diffluent; columella spherical, ellipsoidal to cylindrical, about 40 μm wide, with apophysis. Sporangiospores were hyaline, smooth-walled, very variable, mostly subspherical to ellipsoidal, 3 ‒11 × 2 ‒7 μm. Chlamydospores abundant and occur in hyphae and sporangiophores (Reproduced from Luet. al [2013])2.
One of the distinguishing characters of Mi is possessing irregularly shaped columellae3.
Microscopic Features
Sporangiospores from M. irregularis (Scale bar = 10um)(reproduced from Lu, X. et. al [2013])2
Sporangiophore, columella, and sporangiospores of Mucor irregularis (scale bar = 250 um) (reproduced from Hemashettar, B. M. et. al)4
Sexual reproduction has been demonstrated in M. irregularis in culture, between clinical isolates from China, and the USA5
M. irregularis has been isolated from soil, plant material, dung, and from 17 human patients with cutaneous infection2.It primarily occurs in Asia2.
First reported as a human pathogen in China in 1991, M. irregularis has been identified as an emerging human pathogen, with 16 subsequent cases reported, including one case each from Japan, India, and USA2. To date, no M. irregularis infections have been fatal.
In contrast to other human pathogens in the Mucorales that are opportunistic and typically cause acute and often fatal infections, M. irregularis infection has tended to occur in apparently healthy, immunocompetent hosts2. Reported cases have involved chronic (1-18 yrs) disfiguring infection of cutaneous and subcutaneous tissue, with no reports of fatalities to date6. Symptoms include swelling, ulceration, and destruction of skin especially of the face, and extremities7. Its unique infection pattern and phylogenetic distance from other human pathogens in the Mucorales indicates a de novo emergence of a human pathogenicity2.
Treatment
M. irregularis infections have been successfully treated with amphotericin B, and some strains have been shown to be sensitive to AmB, but resistant to other antifungals6.
In vitro studies suggest combinations of antifungals such as terbinafine, itraconazole, and amphotericin B, act synergistically, possibly by acting on different targets of ergosterol biochemistry7.
Zygymycoses caused by M. irregularis infection of facial tissue (reproduced from Lu, X. et. al [2009]6[top], and Hemeshettar, B. M. et. al [bottom]4)
Mucor irregularis (formerly Rhizomucor variabilis) is a Zygomycete fungus primarily found in Asia.It has been isolated from soil, dung, from plant material as an endophyte, and as a human pathogen, causing cutaneous infection often in healthy, immunocompetent hosts.It is the source of several novel secondary metabolites including the chlorinated indole-terpenes, Rhizovarins, and cyclic heptapeptides, Unguisins.
Conventional understanding maintains a general inability of Zygomycete fungi to produce secondary metabolites8.There are even cases where secondary metabolism in Zygomyctes is outsourced to a bacterial symbionts.This is the case, for example, with the tubulin-binding, anti-mitotic agent, rhizoxin, which was originally isolated from the Zygomycete fungus, Rhizopus microsporus, assumed to be the producer. Later it was determined to be the product of its bacterial endosymbiont, Burkholderia rhizoxina9.
Genome mining has revealed a modest genetic capacity for secondary metabolite biosynthesis in diverse Zygomycete clades8.
Genome mining of M. irregularis revelaed the presence of several secondary metabolite gene clusters, including at least four, terpene related biosynthetic gene clusters10. Several new secondary metabolites including terpenes and peptides have recently been reported from endophytic isolates of M. irregularis.The Rhizovarins, A-F, are structurally complex, indole-terpenes that were discovered a Mucor irregularis strain isolated from mangrove plant Rhizophora stylosa collected in Hainan Island, China10. This family is structurally related to the penitrems, which are potent neurotoxins produced by fungi in the Ascomycota, including Penicillium10, and Aspergillus11.The rhizovarins are unique however, in containing an acetal linked to a hemiketal, and an eight-membered cyclic ether10.A few of the rhizovarins showed activity (micromolar IC50 values) against HL-60 (human leukemia) and A549 (human lung adenocarcinoma) cell lines10.
Rhizovarin A
New and known unguisins were reported from a M. irregularis strain isolated from the medicinal plant, Moringa stenopetala collected in Cameroon12. Unguisins are a family of cyclic heptapeptides that were first reported from a Emericella unguis isolated from a jellyfish (12,13). They have several unique structural features including the incorporation of non-proteinogenic amino acids; beta-methyl-phenylalanine, and gama aminobutryic acid (GABA), the only cyclic peptide natural products known to include these14. These as well as abundant d-amino acids are suggestive of biosynthesis by non-ribosomal peptide synthetase13. No significant biological activity has yet been reported for unguisins.
Unguisin E
The overlapping chemotypes of Mucor irregularis and distantly related fungi in the Ascomycota is suggestive of one or more horizontal gene transfer events.
Mucor irregularis (Zheng) Stchigel, Cano, Guarro & Ed. Álvarez 2011
(=Rhizomucor variabilis)
Described first from a clinical isolate as Rhizomucor variabilis, by Zheng in 1991(Zheng).
M. irregularis was first isolated from China in 1991, in a human host, causing cutaneous infection(Zheng).
Classification
Kingdom: Fungi,
Phylum: Mucoromycota
Subphylum: Mucoromycotina
Order: Mucorales
Family: Mucoraceae
M. irregularis is most closely related to be M. hiemalis, which is a saprobe.Other congeners include M. luteus and M. silvaticus. Phylogenetic analyses were based on sequences of ITS regions, 5.8S rRNA, and 28S rRNA(Lu).
