Scientists have discovered that a common fungus and a common bacterium can together inflict far more severe damage on living tissues than either microorganism can cause alone. The findings of the study were published in the journal Proceedings of the National Academy of Science.
These results suggest that certain mixed infections should be viewed as coordinated assaults, where the danger depends on the specific partners involved, rather than merely on the names listed in a lab report.
In oral cavity tissues and in mice, this destructive partnership continued to manifest when Candida albicans, a fungus typically residing on human mucous membranes, and specific strains of Enterococcus faecalis, a bacterium often found in the gut, appeared together.
Working at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), Professor Ilse Denise Jacobsen documented that only a subset of the bacterial composition contributed to the additional damage.
This distinction refined the findings, as the alliance was not a fixed trait of the species pair, but rather a property of individual strains. It also set clear boundaries for the outcome and directly pointed to the next question: what do these dangerous strains carry that others lack?
One bacterial tool stood out in particular: cytolysin, a toxin that punctures host cell membranes. When bacteria lacked the gene encoding this toxin, the additional damage completely disappeared under laboratory conditions.
After the researchers reintroduced the gene, the harmful effect resumed, linking the damage to this single toxin.
“Not all enterococci are the same,” said Professor Jacobsen.
Under the microscope, the bacteria attached themselves to the fungus rather than moving independently nearby. By traveling along these fungal filaments, the bacteria positioned themselves directly at host cells, where the toxin could strike them from close range.
Close contact mattered because the toxin is most effective when it reaches living membranes before it disperses or becomes diluted. Through this direct attachment, the fungus became not just a companion, but a delivery route for harmful bacteria.
A second mechanism involved food rather than contact, and it was based on the sugar glucose. Since Candida albicans rapidly consumes glucose, nearby host cells lose an easily accessible energy source. Due to this fuel shortage, those cells handled the toxin less effectively, meaning the fungus helped weaken the target before the bacteria delivered the blow.
These two main mechanisms—attachment and sugar depletion—turned an ordinary shared surface into a much more destructive interaction.
On healthy tissues, Candida albicans often behaves as a commensal, a microbe that typically coexists with us harmlessly. In the gut and beyond, Enterococcus faecalis also resides quietly until illness, antibiotics, or the stress of medical intervention gives it an opportunity to emerge.
Problems arise when immunity drops or antibiotics disrupt the balance of microbes in the environment, providing both organisms space to multiply. This situation explains why this alliance is most concerning in organisms already thrown off balance by disease or treatment.
In the study of numerous bacterial samples, only some worsened the combined infection in host cells. Strains without cytolysin not only failed to respond properly but sometimes even mitigated the damage caused by the fungus.
“In this case, the cytolysin-producing variants turned out to be the most dangerous,” thus, according to Jacobsen, the general pattern was formulated.
This difference could help explain why similar lab reports might conceal vastly different risks if doctors overlook the species name.
Within the bodies of mice, the same pattern was observed when the microbes infected tissues lining the oral cavity. Toxin-producing bacteria aggravated the damage caused by the fungus, whereas toxin-free variants had the opposite effect.
Since the animal results matched the findings from cell culture studies, this alliance appeared not merely as a laboratory curiosity. This is important for medicine, because treatments need to be effective in organisms where microbes compete, feed, and attach to tissues.
Hospital samples often list microorganisms individually, but this study shows that their combination can alter the outcome. Relying only on species names might overlook the presence of a toxin-producing strain within the mixture.
In patients with infections of the oral cavity or other mucous membranes, this hidden difference could help explain unusually severe tissue damage. Thus, more accurate diagnosis may depend on determining what each microbe is capable of, rather than just what it is.
Blocking the toxin itself now appears as one practical way to weaken this partnership before it escalates into conflict. Preventing bacterial attachment to fungal cells could also reduce damage by breaking this close delivery route.
Managing sugar stress in vulnerable tissues might also make a difference, although the paper did not test treatments on patients. This line of reasoning is already guiding researchers at the Leibniz Institute toward more targeted treatments for mixed infections, though testing on patients still lies ahead.
Mixed infections are not just a collection of multiple microbes in one place; they can represent coordinated attacks based on attachment, toxins, and low sugar levels. Therefore, monitoring stress levels and adopting a combined approach are becoming increasingly important, even as the search for effective treatments is just beginning.
About the Author
