Thermally Dimorphic Human Fungal Pathogens—Polyphyletic Pathogens with a Convergent Pathogenicity Trait

Sil, Anita; Andrianopoulos, Alex

doi:10.1101/cshperspect.a019794

Cited by 100 publications

(78 citation statements)

References 149 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In many human fungal pathogens, the morphological transition from yeast to hypha plays a central role in pathogenesis [ 1 , 2 ], as demonstrated in the ascomycetes Candida albicans , Penicillium marneffei , Histoplasma capsulatum , Coccidioides immitis , and Paracoccidiodides brasiliensis [ 3 – 6 ]. Different morphotypes also display different levels of pathogenicity in the basidiomycetous fungus Cryptococcus neoformans [ 1 , 7 ], the causative agent of the deadly cryptococcal meningitis [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The lncRNA RZE1 Controls Cryptococcal Morphological Transition

et al. 2015

View full text Add to dashboard Cite

In the fungal pathogen Cryptococcus neoformans, the switch from yeast to hypha is an important morphological process preceding the meiotic events during sexual development. Morphotype is also known to be associated with cryptococcal virulence potential. Previous studies identified the regulator Znf2 as a key decision maker for hypha formation and as an anti-virulence factor. By a forward genetic screen, we discovered that a long non-coding RNA (lncRNA) RZE1 functions upstream of ZNF2 in regulating yeast-to-hypha transition. We demonstrate that RZE1 functions primarily in cis and less effectively in trans. Interestingly, RZE1’s function is restricted to its native nucleus. Accordingly, RZE1 does not appear to directly affect Znf2 translation or the subcellular localization of Znf2 protein. Transcriptome analysis indicates that the loss of RZE1 reduces the transcript level of ZNF2 and Znf2’s prominent downstream targets. In addition, microscopic examination using single molecule fluorescent in situ hybridization (smFISH) indicates that the loss of RZE1 increases the ratio of ZNF2 transcripts in the nucleus versus those in the cytoplasm. Taken together, this lncRNA controls Cryptococcus yeast-to-hypha transition through regulating the key morphogenesis regulator Znf2. This is the first functional characterization of a lncRNA in a human fungal pathogen. Given the potential large number of lncRNAs in the genomes of Cryptococcus and other fungal pathogens, the findings implicate lncRNAs as an additional layer of genetic regulation during fungal development that may well contribute to the complexity in these “simple” eukaryotes.

show abstract

Section: Introductionmentioning

confidence: 99%

The lncRNA RZE1 Controls Cryptococcal Morphological Transition

et al. 2015

View full text Add to dashboard Cite

show abstract

“…The fungus can undergo morphological transition from the yeast form to the hypha form. Like many dimorphic fungal pathogens (3,4), the morphotype of Cryptococcus is tightly linked to its virulence (5,6). To understand the biology and pathology of Cryptococcus, some important genetic factors that regulate yeast-hypha transition have been identified.…”

mentioning

confidence: 99%

Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition

Meng

Fan

Liao

et al. 2018

Appl Environ Microbiol

View full text Add to dashboard Cite

is a major opportunistic fungal pathogen. Like many dimorphic fungal pathogens, can undergo morphological transition from the yeast form to the hypha form, and its morphotype is tightly linked to its virulence. Although some genetic factors controlling morphogenesis have been identified, little is known about the epigenetic regulation in this process. Proteins with the plant homeodomain (PHD) finger, a structurally conserved domain in eukaryotes, were first identified in plants and are known to be involved in reading and effecting chromatin modification. Here, we investigated the role of the PHD finger family genes in mating and yeast-hypha transition. We found 16 PHD finger domains distributed among 15 genes in the genome, with two genes,α and α, located in the mating type locus. We deleted these 15 PHD genes and examined the impact of their disruption on cryptococcal morphogenesis. The deletion of five PHD finger genes dramatically affected filamentation. TheαΔ and αΔ mutants showed enhanced ability to initiate filamentation but impaired ability to maintain filamentous growth. TheΔ and the Δ mutants exhibited enhanced filamentation, while theΔ mutants displayed reduced filamentation. Ectopic overexpression of these five genes in the corresponding null mutants partially or completely restored the defect in filamentation. Furthermore, we demonstrated that Phd11, a suppressor of filamentation, regulates the yeast-hypha transition through the known master regulator Znf2. The findings indicate the importance of epigenetic regulation in controlling dimorphic transition in Morphotype is known to have a profound impact on cryptococcal interaction with various hosts, including mammalian hosts. The yeast form of is considered the virulent form, while its hyphal form is attenuated in mammalian models of cryptococcosis. Although some genetic regulators critical for cryptococcal morphogenesis have been identified, little is known about epigenetic regulation in this process. Given that plant homeodomain (PHD) finger proteins are involved in reading and effecting chromatin modification and their functions are unexplored in , we investigated the roles of the 15 PHD finger genes in mating and yeast-hypha transition. Five of them profoundly affect filamentation as either a suppressor or an activator. Phd11, a suppressor of filamentation, regulates this process via Znf2, a known master regulator of morphogenesis. Thus, epigenetic regulation, coupled with genetic regulation, controls this yeast-hypha transition event.

show abstract

“…Homogentisate is further catabolized or oxidized and polymerized to form pyomelanin [43]. 4-HPPD has been found to be up-regulated in the yeast phase of all dimorphic primary pathogenic fungi [44]. Disruption of the 4-HPPD gene in Talaromyces marneffei results in a mutant that cannot grow and differentiate into yeast inside macrophages [45].…”

Section: Dimorphismmentioning

confidence: 99%

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

Kirkland

Fierer

2018

Virulence

View full text Add to dashboard Cite

Coccidioides immitis and C. posadasii are two highly pathogenic dimorphic fungal species that are endemic in the arid areas of the new world, including the region from west Texas to southern and central California in the USA that cause coccidioidomycosis (also known as Valley Fever). In highly endemic regions such as southern Arizona, up to 50% of long term residents have been infected. New information about fungal population genetics, ecology, epidemiology, and host-pathogen interactions is becoming available. However, our understanding of some aspects of coccidioidomycosis is still incomplete, including the extent of genetic variability of the fungus, the genes involved in virulence, and how the changes in gene expression during the organism’s dimorphic life cycle are related to the transformation from a free-living mold to a parasitic spherule. Unfortunately, efforts to develop an effective subunit vaccine have not yet been productive, although two potential live fungus vaccines have been developed.

show abstract

Thermally Dimorphic Human Fungal Pathogens—Polyphyletic Pathogens with a Convergent Pathogenicity Trait

Cited by 100 publications

References 149 publications

The lncRNA RZE1 Controls Cryptococcal Morphological Transition

The lncRNA RZE1 Controls Cryptococcal Morphological Transition

Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

Contact Info

Product

Resources

About