There is a fungus among us that isn’t just providing opportunities for cheesy rhymes, it’s killing us. Candida auris has even achieved the status of superbug – which means, drug-resistant strains exist and are spreading.
Now a new study has unveiled its secret: C. auris can have sex. It doesn’t just reproduce by splitting into clones.
Why is fungal sex bad? For us at least? Because one strain with a particular resistance gene may mate with another strain with a different resistance gene, and their progeny could be resistant to both drugs.
Happily, fraternizing in this fungus is infrequent, according to Prof. Jianping Xu of McMaster’s Department of Biology, who works with Canada’s Global Nexus for Pandemics and Biological Threats.
But when this microbe is feeling frisky or for whatever reason, sex will ensue, creating the potential for multi-drug-resistant, more virulent strains, Xu and Yue Wang reported in Computation and Structural Biotechnology Journal.
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Doctors around the world have been sounding alarms about drug-resistant Candida auris, which has now spread to more than 50 countries and earned itself the soubriquet of “serious global health threat.”
Like the more familiar Candida albicans, C. auris normally just sits there on your skin doing nothing noteworthy, though both can cause candidiasis, aka thrush or “yeast.” But the drug-resistant form of C. auris, first identified in 2009, has been spreading among immune-compromised, elderly, and otherwise weakened patients in hospitals and can cause fatal systemic infection.
According to the CDC: “More than 1 in 3 patients with invasive C. auris infection (for example, an infection that affects the blood, heart, or brain) die.”
Some C. auris strains have developed resistance to all three main types of antifungals, the CDC adds. And now we learn that inter-microbial sex may be contributing to its development, by the same sort of gene exchanges that happen when we procreate by mating.
Previous studies had sought evidence of sexual reproduction in C. auris but had not been conclusive, Jianping explains: “Our study here presented the actual evidence for sexual activity of this species in nature.”
Just to be clear: bacteria may exchange genetic material using pili (filamentous appendages), and some think that counts as sex. Some don’t think so. In all bacterial cases, proliferation involves the bacterium splitting, creating two identical bacteria. But each may also indulge in gene transfers or otherwise obtain DNA from outside, which result in the kiddie bacteria not being identical.
“Bacterial sex differs from that of eukaryotes in that it is unidirectional and does not involve gamete fusion or reproduction,” as one paper memorably put it.
But this auris fungus is having sex: the genomic analysis of nearly 1,300 strains available on a public database confirmed genetic recombination events, aka sexual activity, the new paper explains. And unlike the fruit fly, C. auris likely isn’t in this for orgasms.
“One of the really complex and puzzling questions about this fungal pathogen is its origin and how it reproduces in nature,” says Xu. “The research tells us that this fungus has recombined in the past and can recombine in nature, which enable it to generate new genetic variants rather quickly.”
When resistant C. auris gains a foothold in a clinical setting, eradicating it is a problem. It lives not only on and in the patients, but in everything they touch – from the bed and curtains to the sink and walls. Infected patients “shed” fungus like demons and common disinfection doesn’t do the trick. Chlorine-based disinfectants are more useful, and hand sanitizer can help too.
Xu and Wang add that in Canada, three of the five known resistant lineages of C. auris have been identified – some in the same hospital. “The mixing of strains in the same hospital, potentially in the same patient, creates an opportunity for them to meet and mate,” he says.
In previous work published in the American Society for Microbiology journal just this March, he and collaborators at the University of Delhi located C. auris on the skin of apples: the Royal Gala and Red Delicious, that had been treated with fungicides to extend shelf life. That is terrible news.
“We hypothesized that stored fruits could serve as a possible selective force for and a transmission reservoir of antifungal-resistant isolates of pathogenic yeasts, including C. auris,” he and that team wrote. And lo, it turned out to be true. Of 62 tested apples, all stored, eight were positive for the foul fungus. But zero C. auris was found on freshly picked apples.
What are we to learn from this? That use of pesticides in agriculture can promote not only the greater good of antibiotic-resistant deadly bacteria but fungicide-resistant fungi, and the latter can have sex and exchange resistance genes, making them even deadlier.
Xu reassures that just as the fungus gained from its genetic recombination capacity, that could work against it if we learn to harness the trait. Having learned that they can recombine in nature, he explains, theoretically we can harness the process in the lab, bringing insight into the genetic controls of virulence and drug resistance, and potentially other traits that make this fungus so dangerous.