Sporangiospore Size Dimorphism Is Linked to Virulence of Mucor circinelloides

PLoS Pathogens

Teun Boekhout¹  Rosa M. Ruiz-Vazquez²  Maria Cervantes²  Santiago R. Torres-Martinez²  Charles H. Li³  Joseph Heitman³  Soo Chan Lee³  Deborah J. Springer³ 

[1] CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands;Departamento de Genetica y Microbiologia, Facultad de Biologia, Universidad de Murcia, Murcia, Spain;Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America

关键词: Genetic loci;    Fungal spores;    Macrophages;    Moths;    butterflies;    Waxes;    Fungal pathogens;    Zygomycetes;    Phylogenetic analysis;   

DOI  :  10.1371/journal.ppat.1002086

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a heterothallic fungus: (+) sex allele encodes SexP and (−) sex allele SexM, both of which are HMG domain protein sex determinants. M. circinelloides f. lusitanicus (Mcl) (−) mating type isolates produce larger asexual sporangiospores that are more virulent in the wax moth host compared to (+) isolates that produce smaller less virulent sporangiospores. The larger sporangiospores germinate inside and lyse macrophages, whereas the smaller sporangiospores do not. sexMΔ mutants are sterile and still produce larger virulent sporangiospores, suggesting that either the sex locus is not involved in virulence/spore size or the sexP allele plays an inhibitory role. Phylogenetic analysis supports that at least three extant subspecies populate the M. circinelloides complex in nature: Mcl, M. circinelloides f. griseocyanus, and M. circinelloides f. circinelloides (Mcc). Mcc was found to be more prevalent among clinical Mucor isolates, and more virulent than Mcl in a diabetic murine model in contrast to the wax moth host. The M. circinelloides sex locus encodes an HMG domain protein (SexP for plus and SexM for minus mating types) flanked by genes encoding triose phosphate transporter (TPT) and RNA helicase homologs. The borders of the sex locus between the three subspecies differ: the Mcg sex locus includes the promoters of both the TPT and the RNA helicase genes, whereas the Mcl and Mcc sex locus includes only the TPT gene promoter. Mating between subspecies was restricted compared to mating within subspecies. These findings demonstrate that spore size dimorphism is linked to virulence of M. circinelloides species and that plasticity of the sex locus and adaptations in pathogenicity have occurred during speciation of the M. circinelloides complex.

【 授权许可】

CC BY