In the Lit: Mechanisms of genome evolution in Candida albicans

The fungus Candida albicans exists as a prevalent commensal and an important opportunistic pathogen that can infect multiple niches of its human host. Recent studies have examined the diploid genome of C. albicans by performing both short-term microevolution studies and comparative genomics on collections of clinical isolates. Common mechanisms driving genome dynamics include accumulation of point mutations, loss of heterozygosity (LOH) events, large-scale chromosomal rearrangements, and even ploidy change, with important consequences for both drug resistance and host adaptation. Evidence for recombination between C. albicans lineages also highlights a role for (para)sex in shaping the species population structure. Ongoing work will continue to define the contributions of genome evolution to phenotypic variation and the role of host pressures in driving adaptive processes.
https://doi.org/10.1016/j.mib.2019.05.001

In the Lit: Seasons of change: Mechanisms of genome evolution in human fungal pathogens

Fungi are a diverse kingdom of organisms capable of thriving in various niches across the world including those in close association with multicellular eukaryotes. Fungal pathogens that contribute to human disease reside both within the host as commensal organisms of the microbiota and the environment. Their niche of origin dictates how infection initiates but also places specific selective pressures on the fungal pathogen that contributes to its genome organization and genetic repertoire.

Recent efforts to catalogue genomic variation among major human fungal pathogens have unveiled evolutionary themes that shape the fungal genome. Mechanisms ranging from large scale changes such as aneuploidy and ploidy cycling as well as more targeted mutations like base substitutions and gene copy number variations contribute to the evolution of these species, which are often under multiple competing selective pressures with their host, environment, and other microbes. Here, we provide an overview of the major selective pressures and mechanisms acting to evolve the genome of clinically important fungal pathogens of humans.
https://www.sciencedirect.com/science/article/pii/S1567134819300309?via%3Dihub

In the Lit: Hemizygosity Enables a Mutational Transition Governing Fungal Virulence and Commensalism

Candida albicans is a commensal fungus of human gastrointestinal and reproductive tracts, but also causes life-threatening systemic infections. The balance between colonization and pathogenesis is associated with phenotypic plasticity, with alternative cell states producing different outcomes in a mammalian host. Here, we reveal that gene dosage of a master transcription factor regulates cell differentiation in diploid C. albicans cells, as EFG1 hemizygous cells undergo a phenotypic transition inaccessible to “wild-type” cells with two functional EFG1 alleles.

Notably, clinical isolates are often EFG1 hemizygous and thus licensed to undergo this transition. Phenotypic change corresponds to high-frequency loss of the functional EFG1 allele via de novo mutation or gene conversion events. This phenomenon also occurs during passaging in the gastrointestinal tract with the resulting cell type being hypercompetitive for commensal and systemic infections. A “two-hit” genetic model therefore underlies a key phenotypic transition in C. albicans that enables adaptation to host niches.
https://doi.org/10.1016/j.chom.2019.01.005

Welcome to Audra Crouch

As we approach Spring and end the year’s rotation cycle we are very excited to welcome Audra Crouch to the Anderson lab! Audra will be spearheading the mycobiome work in the lab. Welcome Audra!

Audra Crouch

Studying the mycobiome in native american populations and determining if shifts in mycobiome is a causation behind rheumatoid arthritis
Position:
Graduate Student
Degree:
University of Lynchburg, BS Biomedical Science and Music Performance Minor

In the Lit: Role of Mediator in virulence and antifungal drug resistance in pathogenic fungi

Mediator complex has recently emerged as an important regulator of gene expression in pathogenic fungi. Mediator is a multi-subunit complex of polypeptides involved in transcriptional activation in eukaryotes, with roles including preinitiation complex (PIC) assembly and chromatin remodeling. Within the last decade, Mediator has been shown to play an integral role in regulating virulence gene expression and drug resistance in human fungal pathogens. In some fungi, specific Mediator subunits have been shown to be required for virulence. In Candida species, duplication and expansion of Mediator subunit encoding genes has occurred on at least three occasions (CgMED15 in C. glabrata and MED2/TLO in C. albicans and C. dubliniensis) suggesting important roles for Mediator in the evolution of these pathogens. This review summarises recent developments in our understanding of Mediator in fungal pathogens and the potential for the development of therapeutic drugs to target Mediator functions.
Curr Genet. 2019 Jan 14. https://doi.org/10.1007/s00294-019-00932-8

A Brisk Start to the New Year

Joining us for the third rotation of the academic year are Peter Brechting and Jacqueline Wong from the Department of Microbiology! Jacqueline is continuing to progress on the mycobiome project and Peter is investigating the gamma-clade members of the TLO expanded gene family.

Peter Brechting

Investigating the functional effects of the TLO genes on mitochondrial gene expression in C. albicans
Position:
Graduate Rotation Student
Degree:
Miami University, B.S. Microbiology, Minor in Economics

Jacqueline Wong

Studying the mycobiome in Native American populations and determining if shifts in mycobiome is a causation behind rheumatoid arthritis
Position:
Graduate Rotation Student
Degree:
University of California, Los Angeles B.S. in Microbiology, Immunology, and Molecular Genetics, Minor in Biomedical Research

In the Lit: The association of mannose binding lectin genotype and immune response to Chlamydia pneumoniae: The Strong Heart Study

Cardiovascular disease (CVD) is an important contributor to morbidity and mortality in American Indian communities. The Strong Heart Study (SHS) was initiated in response to the need for population based estimates of cardiovascular disease in American Indians. This study demonstrates that MBL2 genotype associates with immune reactivity to C. pneumoniae in the SHS cohort. Thus, MBL2 may contribute to the progression of cardiovascular disease (CVD) among American Indians indirectly through pathogen interactions in addition to its previously defined roles.

In The Lit: The Galleria mellonella Waxworm Infection Model for Disseminated Candidiasis

Summary: Galleria mellonella serves as an invertebrate model for disseminated candidiasis. Here, we detail the infection protocol and provide supporting data for the model’s effectiveness.

Dunn, M. J., Woodruff, A. L., Anderson, M. Z. The Galleria mellonella Waxworm Infection Model for Disseminated Candidiasis. J. Vis. Exp. (141), e58914, doi:10.3791/58914 (2018).

Rotations Changing with the Leaves

We are excited to welcome Audra Crouch for the second rotation cycle this year! Audra comes from the Department of Microbiology and is rotating with the ongoing microbiome work in the lab.

Audra Crouch

Studying the mycobiome in native american populations and determining if shifts in mycobiome is a causation behind rheumatoid arthritis
Position:
Graduate Rotation Student
Degree:
University of Lynchburg, BS Biomedical Science and Music Performance Minor

Autumn at Ohio State

With the new academic year fully in motion we welcome Pranav Rana as a rotation student in the lab from the Department of Microbiology!

Pranav Rana

Investigating the role of TLO gene family expansion in C. albicans using CRISPR-mediated gene editing
Position:
Graduate Rotation Student
Degree:
University of Idaho, B.S. Microbiology