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Name

Beta lactones as novel antivirulence treatment against bacteria such as Staphylococcus aureus and MRSA

Organization name

Bayerische Patentallianz GmbH

Profile

Novel antivirulence treatment that prevents resistance development and side effects

Background

Antimicrobial resistances are one of the most serious health threats in the 21st century. Multiresistant pathogens with resistances against all currently known antibiotic classes continuously spread all over the world. However, development of novel antibiotic drugs declines, thereby triggering the need for new concepts to combat the rising medical need in antibacterial treatment. Among multiresistant bacteria Staphylococcus aureus – also called MRSA - is the most prominent pathogen. MRSA causes high numbers of severe and lethal infections both in and outside hospitals. Novel concepts and novel chemical entities are urgently needed to treat MRSA infections and face the rapid resistance development.

Innovation

Beta lactones are synthetically produced small molecules that tremendously reduce the pathogenicity of Staphylococcus aureus and MRSA. They act by inhibiting the caseinolytic protease P (ClpP), a key regulator of multiple virulence
factors. Thereby the production of detrimental bacterial toxins (i.e. hemolysins, toxic shock syndrome toxin, enterotoxins) is prevented resulting in disarming the bacteria during infection. Bacterial killing and clearance can therefore be achieved through the action of the immune system. Importantly, the concept of antivirulence prevents both the biggest challenges
in antibiotic treatment today: resistance development and side effects. This also allows for longer treatment periods.

Commercial Opportunities

Bacterial infections are primarily treated with antibiotics, but meanwhile many bacterial strains are resistant against most available antibiotics. With this new approach here the problem of resistances is avoided resulting in an effective treatment. There are currently other small molecule products under development that have already shown some efficacy in animal models. But in contrast to the beta lactone approach here, the competitive small molecules only impair a small part of the complex regulatory virulence network – just like most of the antibody therapeutics. Beta lactones are suitable for topical treatment of bacterial infections not forsystemic application. Superficial infections that can be addressed are wound infections, impetigo, secondary pyoderma, folliculitis and abscesses. Applications in decolonization and prevention of biofilm formation can also be envisioned.

Developmental Status
  • Beta lactones have been proven to be effective in the inhibition of a broad spectrum of virulence factors in Staphylococcus aureus, Listeria monocytogenes and to act as an antibiotic against mycobacterium tuberculosis.
  • Animal models using S. aureus in severe skin infections have been successful showing the reduction of infectious lesion size with a local application of beta lactones.
  • Broad spectrum efficacy has been demonstrated on 20 clinical isolates of resistant and sensitive Staphylococcal strains.
Patent Status
  • US patent granted
  • National phase EP, JP, IN, CA, ARIPO

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