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Researchers uncover a new antifungal agent among marine bacteria in the Florida Keys.
Fungal infections are responsible for 2 million deaths in a year (Brown et al., 2012). Anti-fungal drugs are used to treat these infections but more recently there has been an increase in multi-drug resistant (MDR) fungi that don’t respond to this treatment. Resistant infections occur when a microbe develops a mutation that allows it to resist treatment by antimicrobial drugs. When an infection develops resistance to multiple drugs MDR (Fairlamb et al., 2016). One particularly vicious MDR fungus, Candida auris has become prevalent among patients in hospital settings. An invasive drug-resistant C. auris infection kills one in three patients (CDC). Currently, there are only three classes of antifungal drugs that are available for treatments. the lack of diversity in antifungal contributes to the danger of resistant fungi (Clardy et al., 2009). With few treatment options present it is easy for fungal strains that are resistant to all treatments. Novel antifungal drugs are essential to limiting the spread of MDR fungal infections.
When searching for new antimicrobial drugs, scientists often turn to natural sources. In their search to uncover a new antifungal agent, researchers examined bacteria samples collected from marine invertebrates. They screened 1482 actinobacteria, a common microorganism, sampled from the area around the Florida Keys to find chemically unique strains. A common problem when screening for novel chemical compounds is finding a lot of similar or already known compounds. To overcome this problem researchers developed a new method of analysis to find novel chemicals produced by bacteria. They found 174 strains with this technique. To further narrow down their results the strain were grown in the presence of the fungus C. albicans. Antifungal agents could be found in the culture that showed little to no significant fungal growth. From this process the researchers discover a new antifungal molecule they named turbinmicin. Turbinmicin was isolated from a bacteria strain associated with a species of sea squirt, Ecteinascidia turbinate.
To test the effectiveness of turbinmicin as an antifungal agent, researchers administered it to a variety of fungal cultures including MDR C. auris. Almost all the fungi were inhibited by as little as .5 µg/ml of turbinmicin. Further experiments were conducted using mice. Mice infected with a drug resistant form of C. auris showed a greatly decreased fungal load after four days of treatment with turbinmicin. In comparison, approved antifungal drugs had almost not effect on fungal load. Researchers also looked at the toxicity of turbinmicin at high doses. Mice given large amounts of turbinmicin did not exhibit and signs of toxicity. This indicates that turbinmicin is not harmful to mammals. These results are promising and demonstrate turbinmicin effectiveness at combating MDR C. auris.
The discovery of a new antifungal agent is very exciting and has the potential to save lives. Turbinmicin is highly effective at inhibiting fungal infections in mice. Human trials still need to be conducted to confirm the efficacy and safety of turbinmicin for use in human patients but the current results seem promising. A drug developed from turbinmicin could prevent deadly infections from occurring in hospitals and clinics around the world. Drug resistance is a larger issue that isn’t limited to fungal infections. Drug resistant bacteria and viruses are also becoming more common and more dangerous. More infections are becoming resistant to typical antimicrobial treatments. The technique that was used to isolate and identify turbinmicin could be applied to find other antimicrobial agents that could be used to fight MDR infections. An expanded study could screen microbes from a larger geographical area with a broader range of focus on all antimicrobial agents instead of specifying antifungals. This could lead to the discovery of new drugs able to treat MDR infections.
References
Brown, G. D., Denning, D. W., Gow, N. A. R., Levitz, S. M., Netea, M. G., & White, T. C. 2012. Hidden Killers: Human Fungal Infections. Science Translational Medicine, 4(165), 165rv13-165rv13. https://doi.org/10.1126/scitranslmed.3004404
Candida auris Information for Patients and Family Members | Candida auris | Fungal Diseases | CDC. 2020, May 29. https://www.cdc.gov/fungal/candida-auris/patients-qa.html
Clardy, J., Fischbach, M., & Currie, C. 2009. The natural history of antibiotics. Current Biology : CB, 19(11), R437–R441. https://doi.org/10.1016/j.cub.2009.04.001
Fairlamb, A. H., Gow, N. A. R., Matthews, K. R., & Waters, A. P. 2016. Drug resistance in eukaryotic microorganisms. Nature Microbiology, 1(7), 16092. https://doi.org/10.1038/nmicrobiol.2016.92
Zhang, F., Zhao, M., Braun, D. R., Ericksen, S. S., Piotrowski, J. S., Nelson, J., Peng, J., Ananiev, G. E., Chanana, S., Barns, K., Fossen, J., Sanchez, H., Chevrette, M. G., Guzei, I. A., Zhao, C., Guo, L., Tang, W., Currie, C. R., Rajski, S. R., … Bugni, T. S. 2020. A marine microbiome antifungal targets urgent-threat drug-resistant fungi. Science, 370(6519), 974–978. https://doi.org/10.1126/science.abd6919
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