Harnessing random peptide mixtures to combat multidrug-resistant fungal infections | mBio The rising prevalence of invasive fungal infections, particularly among immunocompromised individuals, has become a critical public health concern. However, antifungal drug development has not kept pace with this growing need, and treatment options remain limited to a small number of drug classes. The emergence of multidrug-resistant fungal pathogens, such as Candida auris, further exacerbates this crisis by reducing the efficacy of existing therapeutics and increasing the risk of treatment failure. In this study, we evaluate the antifungal potential of FK20, a random peptide mixture (RPM) composed of L-phenylalanine and L-lysine. FK20 displays potent activity against C. auris and other clinically relevant Candida species, impairs biofilm formation, and exhibits synergy with caspofungin. Importantly, FK20 limits the emergence of resistance and demonstrates therapeutic efficacy in a murine model of systemic candidiasis. These findings establish RPMs as a promising new class of antifungals with broad-spectrum activity and clinical potential against drug-resistant fungal infections.

🚨A random solution to a growing fungal threat🚨
Our work on random peptide mixtures reveals potent antifungal activity against multidrug-resistant pathogens like C. auris, with low resistance potential and strong biofilm activity.
Now out in mBio!
Congrats to John and Yael for the fantastic work 👏

If I'm not mistaken, they gound that the virus induce TLR3-mediated interferon respinse?

transmission is strictly intracellular, so they’re entirely dependent on the fungus for survival.

Great question! There are quite a few mycoviruses in plant pathogenic fungi that can weaken virulence, but as far as I know, none that outright kill their fungal host. Unlike most viruses, mycoviruses don’t have an extracellular phase

Intriguing idea! now if only the funding agencies loved it as much as the fungi do 😂

Mycoviruses steer fungal fitness Nature Microbiology - A mycovirus drives the fitness of the lung-infecting fungus Aspergillus fumigatus under stress, helping it to survive within immune cells, and thus shaping its pathogenesis.

Our study on a mycovirus that boosts fungal virulence is now out — and beautifully covered in this Behind the Paper piece by Amariliz Rivera

Huge thanks for capturing the heart of the story so thoughtfully. @natmicrobiol.nature.com rdcu.be/eB9yg

VERY INTERESTING

AfuPmV-1M, a dsRNA mycovirus in 𝘼𝙨𝙥𝙚𝙧𝙜𝙞𝙡𝙡𝙪𝙨 𝙛𝙪𝙢𝙞𝙜𝙖𝙩𝙖𝙨, boosts fungal stress tolerance, melanin, virulence

In vivo, antiviral (ribavirin) treatment cut viral load and improved mouse survival—mycoviruses are hidden “backseat drivers” of fungal disease

www.nature.com/articles/s41...

I thought the Aspergillus fumigatus pan-genome was pretty wild when we started this project.

Aspergillus flavus said, "hold my beer..." Not only does it have a strong population structure with differences between environmental and clinical strains, only 58%of genes are conserved across the species!

Such a great story! A pathogen within a pathogen 🤯. Made me think of all Totiviridea family that infect protozoan parasites including Trichomonas vaginalis and Giardia lamblia. Always wondered if Tryps have these too and whether the pathology is partly due to a hidden bug.

Mazal tov Professor 🫡

Thanks so much, Marc! 🙏
This work was very much inspired by your phenomenal studies on yeast mycoviruses. We’re standing on your shoulders here 💪

4 years ago I was honored to host the legendary Elio Schaechter in the microbiology journal club, when he was only 93 yo...
Elio told us about very peculiar microbes that travel 1 mm/sec, reside inside mitochondria, ride a microbial bus...He named my kids who also joined "micro microbiologists"
RIP

Thanks @seanaduggan.bsky.social 🙏

💰 And of course, thanks to
@erc.europa.eu , CIFAR,
and the Zuckerman STEM Leadership Program
— without your support, this story would still be stuck in our grant drafts 🎯

✨ @laurafabre.bsky.social & @ameliabarberphd.bsky.social — for brilliant support, sharp insights, and being the kind of collaborators everyone wishes they had
Couldn’t have done it without you — and honestly, wouldn’t have wanted to 🎯

🎉 Mega thanks to:
✨ Vanda Lerer — for boldly launching this exciting line of research
✨ Marina Rocha — for expertly steering this project and bringing it triumphantly across the finish line
✨ John Adeoye & all Shlezinger lab members — for your unwavering support and teamwork at every stage ⬇️

So maybe the next time someone has a fungal infection, the question shouldn’t just be “Which fungus?” but also “Which virus is it carrying?"

And speaking of things riding along — time to thank the amazing people who made this journey possible 👇

Why does this matter?
🧪 Mycoviruses are barely on the radar in human disease.
Our work shows they:
✔️ Shape fungal virulence
✔️ Influence host–pathogen interactions
✔️ Could be diagnostic markers
✔️ May be therapeutic targets ⬇️

💡 Therapeutic twist:
We treated infected mice with antivirals during fungal infection.
Result?
📉 Lower mycovirus load
📈 Higher mouse survival
Suggesting that targeting the virus could be a new way to fight fungal disease. ⬇️

When we “cured” the fungus of its virus, it:
⬇️ Made fewer spores
⬇️ Produced less melanin
⬇️ was less stress resistant
⬇️ Was less virulent in mice
Turns out, the virus helps the fungus fit the harsh environment of the host. ⬇️

Our culprit: AfuPmV-1M, a dsRNA virus that’s set up permanent residence inside A. fumigatus. Turns out this isn’t just a harmless hitchhiker- it’s wired into the regulation of key fungal processes, boosting heat resistance, dodging oxidative bursts, and helping the fungus thrive in mouse lungs. ⬇️

Meet Aspergillus fumigatus — responsible for ~65% of all invasive fungal infections in humans, with mortality rates up to 50%.
We asked: could a mycovirus (a virus that infects fungi) be quietly steering fungal disease in humans?⬇️

Aspergillus fumigatus dsRNA virus promotes fungal fitness and pathogenicity in the mammalian host - Nature Microbiology A mycovirus infecting the pathogenic fungus Aspergillus fumigatus enhances its stress tolerance and virulence in mice.

🚨 Fungi + viruses + mammalian lungs? Buckle up! Our new paper in
@natmicrobiol.nature.com
uncovers the story of a deadly fungus and its gnarly viral hitchhiker — and how this duo may change how we diagnose & treat fungal disease 🍄🫁🚨 doi.org/10.1038/s415... ⬇️