Breaking down the microbiology world one bite at a time
Solanimycin: The new antifungal in town
We have all been infected with bacteria or fungi at some point, and many of us have miraculously and swiftly recovered thanks to antibiotics. But some have not been so lucky; despite taking antibiotics, their infection persists. Why do you think this is so?
The occurrence of antimicrobial resistance has been increasing at alarming rates over the past few decades. In fact, WHO declares antimicrobial resistance as one of the 10 top primary threats to public health. Briefly, antimicrobial resistance occurs when the microbes defeat the very drugs that were designed to kill them (CDC 2022).
Antifungal resistance, now seen in 19 fungal species (!), is an underrepresented element of antimicrobial resistance. The WHO warns that over-using antifungal agents, especially in agriculture and aquaculture, propagates the spread of drug-resistant fungi. In agriculture, for instance, antifungal resistance already threatens 80% of active fungicides. These fungicides are already used to protect crops and account for ~77% of the global market! Can you imagine the loss if the antifungals wouldn’t work anymore? And yet, despite the obvious need, naturally derived antifungal compounds have been far less developed than their antibacterial counterparts, as observed over the past 40 years.
Out of the ~217 000 bacterial genomes investigated, only ~3% of the genes with a potential for the production of secondary metabolites have been explored experimentally so far. Based on the data, plant-associated proteobacteria show the most promise in producing new bioactive natural products such as antifungals. Amongst these bacteria, Dickeya solani was spotted and explored and with it, solanimycin made its debut.
The bacteria in question…
Dickeya solani, previously known as Pectobacterium or Erwinia chrysanthemi, is an emerging plant pathogen, which has made its name among the list of top ten pathogens! This “picaroon” is notoriously infamous for causing blackleg and soft rot in potato plants (Solanum tuberosum). Basically, the bacterium is a Gram-negative, motile, non-springing, straight rod-shaped cell with rounded ends.
Within itself, this bacterial phytopathogen carries various secondary metabolite gene clusters, often giving rise to products like antifungals and anti-oomycetes (FYI: oomycetes are not fungi but are susceptible to conventional fungicides) like oocydin A, antimicrobial pigment indigoidine and so on.
… The antibiotic and its secondary metabolism
In bacteria, gene clusters encode bioactive compounds and their synthesis makes up to ~14% of the bacterial genomic content. Solanimycin is one such bioactive compound that acts as a broad-range antifungal.
Of the secondary metabolites in the bacterium, polyketides (PKs) and nonribosomal peptides (NRPs) form two of the largest families. The bacterium D. solani uses a similar hybrid polyketide/nonribosomal peptide (PKS/NRPS) system to produce its secondary metabolite: solanimycin.
The core machinery of this solanimycin (sol) gene cluster consists of SolA as PK and three NRPs in the form of SolF, SolG, and SolH. Together, they are involved in various activities including immunosuppression, anticancer and antimicrobial activities. Of these genes within the cluster, one encodes for the production of So1L, the protein that secretes the metabolite (antibiotic) to the outer environment.
In addition, solanimycin production is regulated by two quorum-sensing systems of the bacteria: ExpIR acyl-homoserine lactone and vfm. These quorum sensing systems (QS) enable the bacterium to adjust its gene expression (and thus antifungal secretion) through chemical signal molecules, depending on cell density. The first system, typically found in Gram‐negative bacteria, recognises N‐acyl‐homoserine lactones. They are important signalling molecules that enable the bacterium to interact with eukaryotes (plants). The second QS modulates the virulence factor, vfm, which plays an important role in metabolite production.
Interestingly, solamycin production in the bacterium intensifies in conditions that mimic the plant-host environment, and works effectively, particularly against Candida albicans – the infamous human pathogen causing candidiasis (You can read about this infection here).
In their study, scientists studied the antagonistic behaviour of the compound on 26 phytopathogenic fungi (plant-pathogens). These fungi belonged to 5 different classes and 12 orders, and even included those ranking in the top 10 of the “bad guys” list! And guess what? Solanimycin, in its true heroic fashion, vanquished around 70% of the tested pathogens! (Nicely done, don’t you agree?)
The susceptible fungi included Armillaria mellea, Botrytis allii, Botrytis cinerea, Botrytis fabae, Fusarium culmorum, Helminthosporium sativum, Monilinia fructigena, Mycosphaerella graminicola, Pyrenophora graminea, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Rhizoctonia solani and Candida albicans (say: goodbye, candidiasis!) which are infamously identified for causing economic losses.
Amazingly, the researchers found no effect of solanimycin on bacteria when they tested it in worms infected with certain bacteria associated with diseases. This circles back to the main finding that solanimycin vehemently targets fungi, and not bacteria.
Furthermore, antifungal production varied among different nutritional sources. For instance, high solanomycin production was particularly observed in a medium that mimics the environment of potato tubers with respect to pH and nutrient levels. This medium is potato dextrose agar, and the bacterial growth in this medium confirms its presence as the infamous pathogen dreadful to potato plants.
… Importance of this study
All things considered, this study essentially bolsters the potential of plant-associated bacteria regarding finding new antimicrobials.
As shown above, the production of secondary metabolites- such as antifungals – in the lab can be very complex, cryptic and frankly, energy demanding, with the pathways often not well understood.
Therefore, in order to overcome this, scientists have mimicked environmental conditions prompting the activation of those antifungal clusters (cue in — the culture media that mimics potato tubers) which prefer to otherwise remain shrouded in mystery. One could definitely wonder how many more valuable bioactive gifts these bacteria conceal from us so mystically and how we could find them…
Link to the original post: Matilla, M. A., Monson, R. E., Murphy, A., Schicketanz, M., Rawlinson, A., Duncan, C., & Salmond, G. P. (2022). Solanimycin: Biosynthesis and Distribution of a New Antifungal Antibiotic Regulated by Two Quorum-Sensing Systems. Mbio, e02472-22.
Featured image: Original image using biorender.com, picryl.com, clipart-library.com and craiyon.com