Beer, doughnuts, and genetics textbooks have one thing in common: they were all made possible by collaborations between humans and yeast. Our fungal ally Saccharomyces cerevisiae resides not only in breweries, bakeries, and laboratories, but also sometimes in our own bodies—where, on rare occasions, it betrays us.

S. cerevisiae is increasingly being reported as an opportunistic human pathogen, sometimes even in non-immunocompromised people. Infections remain rare overall, but studying them presents an exceptional opportunity to understand how benign fungi can turn destructive. Such lethal transformations are more common in some other fungi, but those species are often difficult to grow and manipulate in the lab. In contrast, the long history of S. cerevisiae use in laboratory research means there are many powerful tools for working with the species. If baker’s yeast and other fungi become pathogenic through similar mechanisms, understanding S. cerevisiae infections could have broad implications.

With this in mind, Phadke et al. searched for traits that allow S. cerevisiae to invade a model host: the larval form of the greater wax moth Galleria mellonella. This moth is often used in studies of innate immunity, and because it doesn’t naturally cohabitate with S. cerevisiae, the yeast shouldn’t have any preexisting adaptations that would allow it to infect the moth. This means investigating how yeast infect it can inform researchers about fungal pathogenesis in general.

Comparing yeast strains derived from clinical samples to ones from environmental samples revealed that strains from both groups were equally likely to be pathogenic in the moths. Although this conflicts with findings in mice that clinically isolated strains are more likely to be pathogenic, the studies do concur that pathogenic strains are more likely to be able to form pseudohyphae—elongated strands of cells that remain joined after cell division.

The researchers used a library of yeast deletion mutants to screen for strains that grow better or worse in the moth larvae than in standard conditions. They noticed that one strain that struggled to infect the moths lacked the gene slt2, which encodes a protein that helps maintain part of the yeast’s cell wall. This part of the cell wall normally shields fungal molecules that the host could recognize. If these molecules were noticed by the moth immune system, it could cause a defensive response against the yeast, providing a possible explanation for the strain’s inability to infect the moths. This finding aligns with previous observations that cell wall integrity genes are important for other opportunistic fungal pathogens to infect hosts.

Several genes encoding mitochondrial proteins were also more important for yeast growing in the moth larvae than they were for cells growing in vitro, but since mitochondria have so many roles in the cell, it’s difficult to say how exactly these genes affect pathogenesis. The screen also turned up genes involved in metabolism of some aromatic compounds. In most cases, strains with one of these genes deleted grew better in the moths than they did in vitro, indicating that the genes aren’t important for pathogenesis—but two strains suffered dramatic fitness hits. Both strains were mutant for genes required for the synthesis of two aromatic amino acids, tyrosine and phenylalanine. In mice, S. cerevisiae infection is greatly attenuated if the yeast cannot synthesize aromatic amino acids, and infection in the moths may be similar in this regard.

This work asserts that some of the genetic underpinnings of pathogenesis are shared among S. cerevisiae and other fungal opportunistic pathogens and fuels hope for development of a broad-spectrum treatment targeting numerous fungal infections. It also demonstrates the power of our alliances with laboratory models—even when they go on the attack.

CITATION:

Phadke, S.; Maclean, C.; Zhao, S.; Mueller, E.; Michelotti, L.; Norman, K.; Kumar, A.; James, T. Genome-Wide Screen for Saccharomyces cerevisiae Genes Contributing to Opportunistic Pathogenicity in an Invertebrate Model Host.
G3, 8(1), 63-78.
DOI: 10.1534/g3.117.300245
http://www.g3journal.org/content/8/1/63

, , , , , ,

Nicole Haloupek is a freelance science writer and a recent graduate of UC Berkeley's molecular and cell biology PhD program.

View all posts by Nicole Haloupek »

Read more in

  • Collage of 2021 Rosalind Franklin Award recipients

    Where are they now? Rosalind Franklin Young Investigator Award recipients share updates on their research

    Rosalind Franklin Young Investigator Award applications are open–make sure you submit your application or nomination of a colleague by September 30, 2024.

  • University of Minnesota researchers map genome of the last living wild horse species

    The study, published in G3: Genes|Genomes|Genetics, is part of larger conservation efforts to save Przewalski’s horse.

  • Congratulations to the Spring 2024 DeLill Nasser Awardees!

    GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Spring 2024! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…

  • Carolyn Damilola headshot

    Carolyn Damilola: an NFS Rising Scientist on a lifelong quest to learn more

    Carolyn Damilola is an NFS Rising Scientist from Nigeria doing respiratory system research and paving the way for scientists from underrepresented communities through mentorship.

  • Text over a blue background image: Apply for up to $2,000 for your project from the Starter Culture Microgrant Program.

    What does a good microgrant proposal look like?

    Members of the Microgrant Review Committee share their tips for a successful proposal.

  • A blurred image of a human face is shown against a dark background.

    The first piece of the facial recognition puzzle

    New research in GENETICS gives a first peek at the molecular pathway involved in recognizing faces.

  • New Senior Editor Amy MacQueen joins GENETICS

    A new senior editor is joining GENETICS in the Genome Integrity and Transmission section. We’re excited to welcome Amy MacQueen to the editorial team.

  • Close up of an adult zebrafish with blue and white stripes in an aquarium with red lighting.

    Block party on the zebrafish sex chromosome

    Research in G3 identifies a gene regulatory block of the zebrafish genome responsible for overseeing the maternal-to-zygotic-transition.

  • Lemna Minor, the common duckweed

    Unraveling the mysteries of duckweed: epigenetic insights from Spirodela polyrhiza

    Research published in G3 offers insight into the impact of DNA methylation on clonal propagation in asexually reproducing plants.

  • Luciano Marraffini headshot

    A microbiologist’s quest to understand CRISPR in bacterial self-defense

    2024 Genetics Society of America Medal recipient Luciano Marraffini determined how CRISPR-Cas systems destroy genetic targets with precision, paving the way for gene editing technology development.

  • Elaine Ostrander headshot

    Unlocking mysteries of trait and disease heritability in dogs

    2024 Edward Novitski Prize recipient Elaine Ostrander, a pioneer of the domestic dog model, discovered numerous genes affecting dog size, morphology, behavior, and disease susceptibility—many of which have relevance in humans.

  • NSF-funded BIO-LEAPS Grant to Support Culture Change in Genetics

    GSA and collaborators Personal Genetics Education & Dialogue and Reclaiming STEM Institute launch NSF-funded BIO-LEAPS project to support culture change in genetics 

    We are thrilled to announce that the Genetics Society of America (GSA) is collaborating with the Personal Genetics Education & Dialogue (PGED) based in the Department of Genetics at Harvard Medical School, and the Reclaiming STEM Institute (RSI) on a Leading Culture Change Through Professional Societies of Biology (BIO-LEAPS) grant from the U.S. National Science…

  • Daman Saluja: Navigating Science and Policy in India

    In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the GSA Early Care­er Scientist…

  • Deborah Andrew headshot

    A fly geneticist’s journey into discovering rules of organ development

    2024 George W. Beadle Award recipient Deborah Andrew discovered new genes and pathways in Drosophila salivary gland organogenesis. Now, her work can help optimize cell secretion in therapeutic applications and fight malaria.

  • Małgorzata Gazda's headshot

    Małgorzata Gazda: How receiving the DeLill Nasser Award helped her land her dream job

    Have you ever experienced an event that changes the course of your life, or in this case, your career? Małgorzata (Gosia) Gazda is Assistant Professor at the University of Montreal and in 2022, she received the DeLill Nasser Award for Professional Development in Genetics, which she used to attend and present at the 2022 Population,…

  • Hongyu Zhao joins GENETICS as new Senior Editor

    A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team.

  • Julio Molina Pineda at TAGC 2024

    GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024 

    “At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…

  • Early Career Leadership Spotlight: Olufemi Osonowo

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Olufemi Adekunle OsonowoCareer Development SubcommitteeDalhousie University Research Interest Metabolomics and genomics are two distinct but complimentary approaches that offer valuable insights into the underlying mechanisms of complex traits, such…

  • Early Career Leadership Spotlight: Hector Mendoza

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Hector MendozaCommunication and Outreach SubcommitteeUniversity of Michigan Research Interest My research goals converge around the evolution of sexual reproduction. During my doctoral program, I investigated mitochondrial inheritance, a mechanism…

  • Paths to Science Policy with Daniel Pomeroy

    In this interview, we sat down with Daniel Pomeroy. Daniel is currently the Executive Director of the Scientific Policy Initiative at Harvard. He has a wide history of science policy involvement. We discussed his journey into the science policy space and also resources for early career scientists interested in science policy. Would you provide a…