Abstract
The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. More than half of the tested strains (27) were identified as active in at least one assay. The rare earth salt lanthanum chloride (LaCl3) was shown to be as an effective elicitor. Among the 27 strains, the anti-microbial activity of 15 were induced or enhanced by the addition of LaCl3. This part of study focused on one strain R818, in which potent antifungal activity was induced by the addition of LaCl3. We found that the LaCl3-activated metabolites in R818 are likely antimycin-type compounds. One of them, compound 1, has been purified. Spectroscopic analyses including HR-MS and 1D NMR indicated that this compound is urauchimycin D. The antifungal activity of compound 1 was confirmed with a minimal inhibitory concentration (MIC) of 25 μg/mL; the purified compound also showed a moderate activity against C. difficile. Additional notable strains are: strain N217 which showed both antifungal and antibacterial (including P. aeruginosa) activities and strain M864 which showed potent activity against C. difficile with an MIC value (0.125 μg/mL) lower than those of vancomycin and metronidazole. Our preliminary studies show that deep-sea actinobacteria is a promising source of anti-infective natural products.
Highlights
Infectious diseases remain a major threat to human health, annually causing millions of deaths worldwide, especially in medically less-developed countries and regions (Spellberg et al, 2008)
We focused on actinobacteria isolated from deep-sea sponges and aimed to find novel anti-microbial natural products
In an effort to prospect these marine actinobacteria for novel anti-infective natural products and to optimize the approach for compound production, 50 strains from the Harbor Branch Oceanographic Institute (HBOI) collection were used in this study, all of which were cultivated from marine sponges
Summary
Infectious diseases remain a major threat to human health, annually causing millions of deaths worldwide, especially in medically less-developed countries and regions (Spellberg et al, 2008). Current antibiotics are losing their capacity to treat infectious diseases, and pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus have again become fatal threats. Both the United States Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have issued lists of priority pathogens: the CDC listed 18 drug-resistant bacteria as threats to the United States; in 2017, WHO listed, for the first time, 12 families of bacteria as the greatest threat to human health. Novel antibiotics are urgently needed to treat disease caused by these pathogens
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