Moenomycin-peptide Complexes to Combat MDR Gram Negative Bacterial Infections
A unique multifunctional approach to expand the spectrum of largely inactive MoeA to target resistant Gram negative bacterial pathogens
Increasing bacterial resistance against currently used antibiotics and the lack of new antibiotics to combat MDR pathogens are major challenges to global health and wealth (estimated 10 million deaths every year by 2050, AMR Review 2014, UK Government). The proposed new antibiotics would address this urgent, clinical need, especially to treat infections arising from MDR Gram negative pathogens. These bacteria, such as Klebsiella pneumonia, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa are listed by the World Health Organisation (WHO) as “high priority pathogens” due to increasing mortality and healthcare burden.
Researchers at The University of Liverpool have pioneered a unique multifunctional approach to expand the spectrum of largely inactive MoeA to target resistant Gram negative bacterial pathogens. MoeA is largely inactive against Gram negative bacteria due to poor delivery through the outer membrane. They successfully expanded the spectrum of MoeA to target Gram negative bacteria in vitro and in vivo. Using a multifunctional approach which brings together two disparate functions, target inhibition (Moenomycin A (MoeA), antibiotic part) and delivery (short non-toxic peptide based delivery systems) through the formation of a single complex or conjugate and its subsequent delivery across the outer membrane. MoeA-peptide combination successfully treated the Pseudomonas aeruginosa infection in murine eye. Their multifunctional antibiotics offer dual benefits; clearing the bacterial infection and minimising the severity of infection (corneal edema (swelling)). It is usually achieved by combing antibiotics and corticosteroids. Their early work indicates that MoeA-peptide complexes operate by a dual mechanism that is antibacterial and anti-inflammatory.
The preliminary clinical indications for MoeA-peptide complex/conjugates are:
- Wound infections, antimicrobial bandages, skin infections
- Eye infections (POC in place), market size USD 7.3 billion, forecasted growth rate CAGR 3.8%
- Hospital-Acquired Bacterial Pneumonia (HABP)/Ventilator-Associated Bacterial Pneumonia (VABP) from Gram positive and Gram negatives using inhalation route. The market size for HABP/VABP is $1.8 billion
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