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The continuous outbreak of drug-resistant bacterial and viral infections imposes the need to search for new drug candidates. Natural products from marine bacteria still inspire the design of pharmaceuticals. Indeed, marine bacteria have unique metabolic flexibility to inhabit each ecological niche, thus expanding their biosynthetic ability to assemble unprecedented molecules. The One-Strain-Many-Compounds approach and tandem mass spectrometry allowed the discovery of a Shewanella aquimarina strain as a source of novel imidazolium alkaloids via molecular networking. The alkaloid mixture was shown to exert bioactivities such as: (a) antibacterial activity against antibiotic-resistant Staphylococcus aureus clinical isolates at 100 µg/mL, (b) synergistic effects with tigecycline and linezolid, (c) restoration of MRSA sensitivity to fosfomycin, and (d) interference with the biofilm formation of S. aureus 6538 and MRSA. Moreover, the mixture showed antiviral activity against viruses with and without envelopes. Indeed, it inhibited the entry of coronavirus HcoV-229E and herpes simplex viruses into human cells and inactivated poliovirus PV-1 in post-infection assay at 200 µg/mL. Finally, at the same concentration, the fraction showed anthelminthic activity against Caenorhabditis elegans , causing 99% mortality after 48 h. The broad-spectrum activities of these compounds are partially due to their biosurfactant behavior and make them promising candidates for breaking down drug-resistant infectious diseases.

Staphylococcus aureus is a Gram-positive opportunistic human pathogen responsible for severe infections and thousands of deaths annually, mostly due to its multidrug-resistant (MDR) variants. The cell membrane has emerged as a promising new therapeutic target, and lipophilic molecules, such as biosurfactants, are currently being utilized. Herein, we evaluated the antimicrobial activity of a rhamnolipids mixture produced by the Antarctic marine bacterium Pseudomonas gessardii M15. We demonstrated that our mixture has bactericidal activity in the range of 12.5-50 µg/mL against a panel of clinical MDR isolates of S. aureus , and that the mixture eradicated the bacterial population in 30 min at MIC value, and in 5 min after doubling the concentration. We also tested abilities of RLs to interfere with biofilm at different stages and determined that RLs can penetrate biofilm and kill the bacteria at sub-MICs values. The mixture was then used to functionalize a cotton swab to evaluate the prevention of S. aureus proliferation. We showed that by using 8 µg of rhamnolipids per swab, the entire bacterial load is eradicated, and just 0.5 µg is sufficient to reduce the growth by 99.99%. Our results strongly indicate the possibility of using this mixture as an additive for wound dressings for chronic wounds.

Emerging and re-emerging viruses represent a serious threat to human health at a global level. In particular, enveloped viruses are one of the main causes of viral outbreaks, as recently demonstrated by SARS-CoV-2. An effective strategy to counteract these viruses could be to target the envelope by using surface-active compounds. Rhamnolipids (RLs) are microbial biosurfactants displaying a wide range of bioactivities, such as antibacterial, antifungal and antibiofilm, among others. Being of microbial origin, they are environmentally-friendly, biodegradable, and less toxic than synthetic surfactants. In this work, we explored the antiviral activity of the rhamnolipids mixture (M15RL) produced by the Antarctic bacteria Pseudomonas gessardii M15 against viruses belonging to Coronaviridae and Herpesviridae families. In addition, we investigated the rhamnolipids' mode of action and the possibility of inactivating viruses on treated surfaces. Our results show complete inactivation of HSV-1 and HSV-2 by M15RLs at 6 µg/mL, and of HCoV-229E and SARS-CoV-2 at 25 and 50 µg/mL, respectively. Concerning activity against HCoV-OC43, 80% inhibition of cytopathic effect was recorded, while no activity against naked Poliovirus Type 1 (PV-1) was detectable, suggesting that the antiviral action is mainly directed towards the envelope. In conclusion, we report a significant activity of M15RL against enveloped viruses and demonstrated for the first time the antiviral effect of rhamnolipids against SARS-CoV-2.