A Revised Species Concept for OpportunisticMucorSpecies Reveals Species-Specific Antifungal Susceptibility Profiles

Abstract

Recently, the species concept of opportunistic Mucor circinelloides and its relatives has been revised, resulting in the recognition of its classical formae as independent species and the description of new species. In this study, we used isolates of all clinically relevant Mucor species and performed susceptibility testing using the EUCAST reference method to identify potential species-specific susceptibility patterns. In vitro susceptibility profiles of 101 mucoralean strains belonging to the genus Mucor (72), the closely related species Cokeromyces recurvatus (3), Rhizopus (12), Lichtheimia (10), and Rhizomucor (4) to six antifungals (amphotericin B, natamycin, terbinafine, isavuconazole, itraconazole, and posaconazole) were determined. The most active drug for all Mucorales was amphotericin B. Antifungal susceptibility profiles of pathogenic Mucor species were specific for isavuconazole, itraconazole, and posaconazole. The species formerly united in M. circinelloides showed clear differences in their antifungal susceptibilities. Cokeromyces recurvatus, Mucor ardhlaengiktus, Mucor lusitanicus (M. circinelloides f. lusitanicus), and Mucor ramosissimus exhibited high MICs to all azoles tested. Mucor indicus presented high MICs for isavuconazole and posaconazole, and Mucor amphibiorum and Mucor irregularis showed high MICs for isavuconazole. MIC values of Mucor spp. for posaconazole, isavuconazole, and itraconazole were high compared to those for Rhizopus and the Lichtheimiaceae (Lichtheimia and Rhizomucor). Molecular identification combined with in vitro susceptibility testing is recommended for Mucor species, especially if azoles are applied in treatment.

Updates on the Taxonomy of Mucorales with an Emphasis on Clinically Important Taxa

“…Mucor belongs to the main genera causing mucormycoses [83]. To date, 12 species are known to be involved in infections [36]. Members of the genus predominantly cause cutaneous infections but also disseminated and gastrointestinal manifestations have been reported [2,36].…”

“…To date, 12 species are known to be involved in infections [36]. Members of the genus predominantly cause cutaneous infections but also disseminated and gastrointestinal manifestations have been reported [2,36]. However, the clinical importance of the genus is still not clear because the causative agents of infections are only morphologically identified to the genus level in most cases [83] and might in fact represent the morphologically similar Rhizomucor or Lichtheimia species.…”

Amphotericin B and Other Polyenes—Discovery, Clinical Use, Mode of Action and Drug Resistance

“…Histoplasma capsulatum exhibits very low MICs for AmB, making it a preferred treatment for this pathogenic mold [ 161 , 162 ]. Although AmB resistance is rare for isolates of Mucorales [ 163 , 164 , 165 ], some Rhizopus and Cunninghamella strains show decreased AmB susceptibility [ 103 , 166 ], with one report showing decreased AmB susceptibility in 3 out of 19 and 5 out of 8 isolates tested, respectively [ 167 ].…”

The Evolutionary Significance of RNAi in the Fungal Kingdom

“…In Mucor lusitanicus, formerly known as Mucor circinelloides f. lusitanicus [ 91 ], sRNAs pairing with transposons and derived from the canonical pathway have been detected (see below for a more detailed description of RNAi pathways of this fungus) [ 43 , 92 ]. A recent study discovered the presence of TE sequences surrounding the centromeric area of M. lusitanicus, which seem to be present in all Mucoromycotina species and, thus, were termed as Grem-LINE1 (genomic retrotransposable element of Mucoromycota) [ 34 ].…”