Fungi have become an invaluable source of bioactive natural products, with more than 5 million species of fungi spanning the globe. Fractionation of crude extract of Neodidymelliopsis sp., led to the isolation of a novel polyketide, (2Z)-cillifuranone (1) and five previously reported natural products, (2E)-cillifuranone (2), taiwapyrone (3), xylariolide D (4), pachybasin (5), and N-(5-hydroxypentyl)acetamide (6). It was discovered that (2Z)-cillifuranone (1) was particularly sensitive to ambient temperature and light resulting in isomerisation to (2E)-cillifuranone (2). Structure elucidation of all the natural products were conducted by NMR spectroscopic techniques. The antimicrobial activity of 2, 3, and 5 were evaluated against a variety of bacterial and fungal pathogens. A sodium [1-13C] acetate labelling study was conducted on Neodidymelliopsis sp. and confirmed that pachybasin is biosynthesised through the acetate polyketide pathway.
Screening of several fungi from the New Zealand International Collection of Microorganisms from Plants identified two strains of Penicillium, P. bissettii and P. glabrum, which exhibited antimicrobial activity against Escherichia coli,Klebsiella pneumoniae, and Staphylococcus aureus. Further investigation into the natural products of the fungi, through extraction and fractionation, led to the isolation of five known polyketide metabolites, penicillic acid (1), citromycetin (2), penialdin A (3), penialdin F (4), and myxotrichin B (5). Semi-synthetic derivatization of 1 led to the discovery of a novel dihydro (1a) derivative that provided evidence for the existence of the much-speculated open-chained form of 1. Upon investigation of the antimicrobial activities of the natural products and derivatives, both penicillic acid (1) and penialdin F (4) were found to inhibit the growth of Methicillin-resistant S. aureus. Penialdin F (4) was also found to have some inhibitory activity against Mycobacterium abscessus and M. marinum along with citromycetin (2).
Antimicrobial bioassay-guided fractionation of the endophytic fungi Neofusicoccum australe led to the isolation of a new unsymmetrical naphthoquinone dimer, neofusnaphthoquinone B (1), along with four known natural products (2–5). Structure elucidation was conducted by nuclear magnetic resonance (NMR) spectroscopic methods, and the antimicrobial activity of all the natural products was investigated, revealing 1 to be moderately active towards methicillin-resistant Staphylococcus aureus (MRSA) with a minimum inhibitory concentration (MIC) of 16 µg/mL.
There is a real and urgent need for new antibiotics which are able to kill Mycobacteria. This group of bacteria includes Mycobacterium tuberculosis, a deadly human pathogen that latently infects a third of the world's population. Multi-drug resistant (MDR) and totally-drug resistant (TDR) isolates have also now evolved. Of increasing importance in many countries are the Non-Tuberculous Mycobacteria (NTM), mycobacterial species which are common soil and water contaminants. Many NTM are able to cause chronic lung and skin and soft tissue infections, especially in patients with suppressed immune systems. One example are members of the Mycobacterium abscessus complex. M. abscessus infections are difficult to treat due to antibiotic resistance and new compounds that target this group are much needed.Because of the slow growth of many mycobacterial species, we routinely use luciferase-tagged strains (1) for our assays. As bacteria only produce light when alive, bioluminescence is an excellent non-destructive real-time reporter to assay for anti-mycobacterial activity in microtitre plate formats using a luminometer (2-4) or in vivo using sensitive imaging equipment (5). This protocol is modified from the method described by Dalton et al (4).
There is a real and urgent need for new antibiotics which are able to kill Mycobacteria. This group of bacteria includes Mycobacterium tuberculosis, a deadly human pathogen that latently infects a third of the world's population. Multi-drug resistant (MDR) and totally-drug resistant (TDR) isolates have also now evolved. Due to the difficulties and dangers involved in culturing M. tuberculosis, an airborne Biosafety Level 3 pathogen, fastergrowing, and less pathogenic mycobacterial species are routinely exploited for TB research and anti-mycobacterial drug discovery. M. marinum shares conserved virulence determinants with M. tuberculosis and is a pathogen of ectotherms (fish, amphibians, and reptiles), as well as causing granulomatous skin infections in humans.Because of the slow growth of many mycobacterial species, we routinely use luciferase-tagged strains (1) for our assays. As bacteria only produce light when alive, bioluminescence is an excellent non-destructive real-time reporter to assay for anti-mycobacterial activity in microtitre plate formats using a luminometer (2-4) or in vivo using sensitive imaging equipment (5). This protocol is modified from the method described by Dalton et al (4).
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