Solanimycin- A Story on new Fungicidal Agent Discovery

Solanimycin, produced by a bacteria living inside rotten potatoes has anti-fungal activity.
The increasing demand for drugs against drug-resistant fungal infections has made it an emergency to discover more antifungal agents. Solanimycin is produced by a hybrid PKS/ NRPS system in an enterobacterial pathogen of potato (UnSplash).
The increasing demand for drugs against drug-resistant fungal infections has made it an emergency to discover more antifungal agents. Solanimycin is produced by a hybrid PKS/ NRPS system in an enterobacterial pathogen of potato (UnSplash).
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Fungus grows on almost every surface! In soil, air, and even on the skin of animals and humans. Some of the common infections we see are ringworm nail and skin infections. Some fungal spores even cause respiratory problems like asthma, aspergillosis, etc. Fungal infections affect people with compromised immune systems. Fungal infections are opportunistic. People who are suffering from AIDS, Lupus, or Cancer, and people on immunosuppressants after transplantations, are the most at-risk group for fungal infection. Some day-to-day infections that people suffer are dandruff, athlete’s foot, ringworm, fingernail or toenail infections, thrush, and even vaginitis.

Antifungals are used to stop and kill the growth of fungi. These drugs are called antimycotic agents. They are used to treat some really dangerous fungal infections like Aspergillosis, candidemia, meningitis, histoplasmosis, and rhinosinusitis. 

A rotten potato which is usually soft, dark and very smelly is also the home for many bacteria. Dickeya solani, one such bacteria makes itself at home inside a rotten potato!. Scientists studied this bacteria and found that although it does rots potatoes especially those in northern Europe, but, they also produce a special chemical that kills dangerous fungi.

This is a medical illustration of Blastomyces, the fungus that causes blastomycosis.
(IMAGE:CDC PHIL)
This is a medical illustration of Blastomyces, the fungus that causes blastomycosis. (IMAGE:CDC PHIL)
The increasing demand for drugs against drug-resistant fungal infections has made it an emergency to discover more antifungal agents. Solanimycin is produced by a hybrid PKS/ NRPS system in an enterobacterial pathogen of potato (UnSplash).
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The increasing demand for drugs against drug-resistant fungal infections has made it an emergency to discover more antifungal agents. Solanimycin, is produced by a hybrid system in an enterobacterial pathogen of potato. This fungus killing agent is found in rotten potato!

Solanimycin is an antifungal agent that acts against a broad range of plant-related pathogenic fungal infections. Solanimycin also works on Candida albicans, which is a very common fungal infection in humans. Fungal infections have great importance in terms of clinical, agricultural, and food security.

This is a medical illustration of an azole-resistant fungus, Aspergillus fumigatus, presented in the Centers for Disease Control and Prevention (CDC) publication entitled, Antibiotic Resistance Threats in the United States.
(IMAGE: CDC PHIL)
This is a medical illustration of an azole-resistant fungus, Aspergillus fumigatus, presented in the Centers for Disease Control and Prevention (CDC) publication entitled, Antibiotic Resistance Threats in the United States. (IMAGE: CDC PHIL)

Candida albicans is an opportunistic pathogenic fungus in humans causing oral thrush, invasive infections and candidiasis. Dickeya solani is a notorious plant pathogenic bacterium, which causes soft rot in potatoes. Sadly, the extensive use of antifungal agents, has caused Candida sp. to show drug resistance. Often at times like this, we look to mother nature for the solutions. A recent discovery has unearthed how a natural compound, Solanimycin, released from one pathogen (Dickeya solani) can act as a broad-spectrum antifungal antibiotic, against the action of another pathogen (Candida sp.). This astonishing discovery of the natural antibiotic today, holds great opportunities for tomorrow, as we step into an era of developing nature-based antifungal compounds, to pave the path to future research in drug discovery, biomedicine and microbiology.

Dr Upasana Datta, Advisory Board Member, Department of Research and Development, Uttoran Foundation, West Bengal, India

The production of the Solanimycin is dependent on the density of the cell growth. The process that governs this is known as Quorum sensing.

Quorum sensing also influences:

1.      Virulence

2.      Competence

3.      Biofilm production

4.      Motility

5.      Antibiotic production

Laboratory tests have confirmed that Solanimycin is effective against a large variety of harmful fungus especially helpful to humans.

The increasing demand for drugs against drug-resistant fungal infections has made it an emergency to discover more antifungal agents. Solanimycin is produced by a hybrid PKS/ NRPS system in an enterobacterial pathogen of potato (UnSplash).
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With the identification of this novel antifungal agent from Dickeya sp. Scientists now want to dig further to study and gain knowledge about more diverse antibiotic/antifungal agents that they can obtain from these seemingly innocent sources. (IMAGE: CDC PHIL)
With the identification of this novel antifungal agent from Dickeya sp. Scientists now want to dig further to study and gain knowledge about more diverse antibiotic/antifungal agents that they can obtain from these seemingly innocent sources. (IMAGE: CDC PHIL)

There are many proofs regarding horizontal gene transfer being at work to inherit the gene clusters that produce this anti-fungal agent. The studies on biosynthetic gene clusters show conserved sequences across phylogenetically distant bacterial species. The biosynthesis studies show that the bacteria that produce the antifungal agent have complex regulatory networks.

The production of solanimycin has a high metabolic cost to the bacterial secondary metabolism. The regulatory network that controls the production is difficult to mimic under laboratory conditions, The studies on the bacteria also show tight regulatory control over post-transcriptional mechanisms.

Given its far-reaching and broad range of antifungal activity, scientists have determined it has great potential for application in the agricultural and clinical fields. With the identification of this novel antifungal agent from Dickeya sp. Scientists now want to dig further to study and gain knowledge about more diverse antibiotic/antifungal agents that they can obtain from these seemingly innocent sources.  

References:

1) Matilla MA, Monson RE, Murphy A, Schicketanz M, Rawlinson A, Duncan C, Mata J, Leeper F, Salmond GPC. Solanimycin: Biosynthesis and Distribution of a New Antifungal Antibiotic Regulated by Two Quorum-Sensing Systems. mBio. 2022 Oct 10:e0247222. doi: 10.1128/mbio.02472-22. Epub ahead of print. PMID: 36214559.

2) https://my.clevelandclinic.org/health/drugs/21715-antifungals.

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