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New drug XF-73 "can eliminate superbugs within 5 minutes": UK researchers

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  • Sally Furniss
    Re: New drug XF-73 "can eliminate superbugs within 5 minutes": UK researchers

    XF-73, a novel antistaphylococcal membrane-active agent with rapid bactericidal activity

    1. Nicola Ooi1,
    2. Keith Miller1,
    3. Joanne Hobbs1,
    4. William Rhys-Williams2,
    5. William Love2 and
    6. Ian Chopra1,*

    + Author Affiliations

    1Antimicrobial Research Centre and Institute of Molecular and Cellular Biology, University of Leeds, Leeds, UK
    2Destiny Pharma Limited, Science Park Square, Falmer, Brighton, UK

    1. *Corresponding author. Tel: +44-113-233-5604; Fax: +44-113-233-5638; E-mail:

    * Received May 18, 2009.
    * Revision requested June 18, 2009.
    * Revision received July 10, 2009.
    * Accepted July 26, 2009.


    Objectives XF-73 is a novel porphyrin antibacterial agent previously reported to inhibit a range of Gram-positive bacterial species, including Staphylococcus aureus. Its mode of action is unknown. Using S. aureus as a model organism we sought to examine the basis of its antibacterial activity.

    Methods The effects of XF-73 on the growth and survival of S. aureus SH1000 were investigated by viable count and culture absorbance techniques. Inhibition of macromolecular synthesis and disruption of membrane integrity after exposure to XF-73 were examined by radiolabelling experiments, the BacLight fluorescent dye assay and measurement of K+ and ATP leakage from the cell. The effect of XF-73 on a staphylococcal coupled transcription?translation system was also investigated.

    Results XF-73 was rapidly bactericidal against S. aureus SH1000 and demonstrated more rapid killing kinetics than all other comparator agents when tested at an equivalent multiple (4?) of the MIC. Exposure of S. aureus to XF-73 for 10 min completely inhibited DNA, RNA and protein synthesis. XF-73 had no effect on transcription and translation in vitro. Cells exposed to XF-73 gave a positive response in the BacLight assay, which detects membrane damage. The drug also caused substantial loss of K+ and ATP from the cell, but did not promote bacterial lysis.

    Conclusions XF-73 exhibited rapid membrane-perturbing activity, which is likely to be responsible for inhibition of macromolecular synthesis and the death of staphylococci exposed to the drug.

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  • Sally Furniss
    Re: New drug XF-73 "can eliminate superbugs within 5 minutes": UK researchers

    18th European Congress of Clinical Microbiology and Infectious Diseases
    Barcelona, Spain, 19?22 April 2008

    XF-73, a novel anti-staphylococcal antimicrobial with very rapid bactericidal activity

    Abstract number: P557

    Miller K., Ooi N., Hobbs J.K., Rhys-Williams W., Love W.G., Hayter I., Katila M., Chopra I.

    Objectives: XF-73 is the lead compound in an entirely new class of anti-microbial agents, developed to address the growing and unmet need for prophylaxis and treatment of drug resistant bacteria. It has previously been shown to be highly potent against a range of S. aureus strains including meticillin-sensitive Staphylococcus aureus (MSSA), healthcare associated meticillin resistant S. aureus (HA-MRSA) and community associated meticillin resistant S. aureus (CA-MRSA) strains. XF-73 exerts rapid bactericidal activity and the aim of this study was to further characterise this effect.

    Methods: Time-kill studies for XF-73 were conducted on S. aureus SH1000 at 4x MIC and samples were taken and prepared for scanning electron microscopy. Membrane integrity in the presence of XF-73 was determined using the BacLight assay, which evaluates the ability of propidium iodide to penetrate into the cell following 10 minutes of drug exposure. A luciferin/luciferase assay was performed to quantify XF-73-induced leakage of intracellular ATP.

    Results: SH1000 cell numbers decreased by 4.5 logs following 5 minutes exposure to 4x MIC of XF-73, and by 7 logs following 30 minutes exposure. Scanning electron micrographs following 5 and 30 minutes exposure to XF-73 showed no morphological damage of SH1000 cultures, compared with untreated cells. Nevertheless, treatment for 10 minutes with XF-73 caused complete perturbation of membrane integrity as evidenced by a 100% loss of membrane integrity in the BacLite assay compared to 0% in the absence of XF-73. ATP leakage was not observed following exposure to XF-73.

    Conclusion: The rapid bactericidal activity of XF-73 is not associated with significant cellular lysis. This is consistent with the absence of morphological damage to S. aureus cultures exposed to XF-73 and the lack of leakage of intracellular material (ATP) after a period where cell viability is reduced by 7 logs. Membrane integrity was however perturbed, suggesting that although the cell remained physically intact, the membrane was severely damaged. Investigations are ongoing to elucidate further the mechanism of action of this highly potent and rapidly bactericidal anti-bacterial agent.

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  • Gert van der Hoek
    Re: New drug XF-73 "can eliminate superbugs within 5 minutes": UK researchers

    Some science:

    XF-73, a novel antistaphylococcal membrane-active agent with rapid bactericidal activity.

    XF-70 and XF-73, novel antibacterial agents active against slow-growing and non-dividing cultures of Staphylococcus aureus including biofilms.

    In vitro activity of XF-73, a novel antibacterial agent, against antibiotic-sensitive and -resistant Gram-positive and Gram-negative bacterial species.



    - this is not for all "superbugs", however it looks like a "broad spectrum" drug
    - it will take years before the drug can be used for patients, may be 5 years or more
    - untill now bacteria always found a way to trick new drugs, it seems unlikely any anti-microbal drug will help forever.
    - hospitals still need to intensify strict hygiene
    - doctors and patients still need to stop misusing anti-biotics

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  • New drug XF-73 "can eliminate superbugs within 5 minutes": UK researchers

    New drug XF-73 can eliminate superbugs within 5 minutes: UK researchers

    by Jasmine - September 20, 2010

    UK researchers recently revealed that they have developed a new anti-bacterial drug, named XF-73, which has the potential to eliminate deadly superbugs such as C-Diff and MRSA, within five minutes.

    Researchers explained this drug starts eliminating the deadly superbugs within five of being administered to a patient; its effective as it gives little chance to bacteria to develop any resistance to it.

    C-Diff/Clostridium difficile is a fatal bacterium, which causes intestinal and diarrhea problems in the carrier, while MRSA/Methicillin-resistant Staphylococcus aureus is responsible for causing numerous infections that hardly respond to any treatment.

    Both the infections are acquired by patients in hospital wards.

    Commenting on their new discovery, study-leader professor Ian Chopra from the University of Leeds said in a press statement:

    "Resistance to antibiotics is seriously undermining the ability of the medical profession to treat bacterial infections. Society urgently requires the discovery and development of new anti-bacterial drugs that have a different method of action and minimal potential for the development of resistance. XF-73 fulfils this need. The bactericidal potency of these drugs is remarkable."

    Researchers are hoping that this new drug will be fully ready and available for use in the hospitals within three years to prevent the further spread of the superbugs.

    Researchers findings
    To come to this conclusion, researchers carried out series of tests where carriers of the superbug bacteria had XF-73 gel placed inside their noses.

    They were surprised to find out that within less than five minutes bugs were eliminated with no side-effects.

    Surprisingly, MRSA turned out to be least resistant to the new drug even after 55 repeated exposures in the clinical tests.

    Researchers further added that XF-73, despite being an anti-bacterial drug, works completely different from antibiotics as it breaks down cell walls and causes rapid loss of its vital contents.

    While antibiotics, on the other hand, acts by destroying specific parts of bacteria in order to disable them, which is a long process and can most certainly provide superbugs? sufficient time to develop resistance to the drug.

    Importance of drug in fighting the bacteria
    Medical experts, who are busy searching the possible cure of superbugs, have welcomed this new discovery as they believe that XF-73 might hold the key to prevent the patients from this bacteria in the hospitals worldwide.

    "There is always the fear that bacteria will develop resistance to the only medication available to eradicate MRSA from a patient who carries the bugs,? said Derek Butler, MRSA Action UK.

    He added "We are aware not everyone can be decolonized from MRSA using the present treatment available so this new development of treatment has shown great promise."