A chimeric endolysin to control streptococcal bovine mastitis

Background

Bovine mastitis, an inflammation of the cow’s udder that is usually caused by a bacterial infection, is the most important economic disease affecting dairy cattle. Streptococcus uberis, Streptococcus agalactiae and Streptococcus dysgalactiae are considered a substantial cause of this disease.

Bovine mastitis is the only disease in animal agriculture where the use of critical antibiotics without any restrictions is still allowed due to the lack of alternatives. As a preventive and therapeutic strategy, critical antibiotics (e.g. cefoperazon, cefquinome) are still registered to combat streptococcal bovine mastitis.

Novel alternatives should be able to kill streptococci that are able to penetrate the mammary epithelial cells of the cow’s udder and form biofilms. These two virulence factors allow these pathogens to circumvent antibiotic therapy, chronically persist and reoccur after treatment. Furthermore, said alternatives should not generate antimicrobial resistance and should be active in raw cow’s milk.

Bacteriophage-derived endolysins (“enzy-biotics”) are increasingly gaining attention due to their specificity, high killing efficacy, unlikely resistance development and rapid degradation in the environment.

Target market

Bovine mastitis remains a very important disease for the dairy industry with an estimated cost of about 450 euro per clinical mastitis case. Its associated global economic cost is estimated between 20 and 30 billion euro per year.

The overall bovine mastitis market is substantial and was estimated at 0.4 billion in North America in 2019 (approximately 9 million dairy cows). If we extrapolate this number it must be close to 1.1 billion for the EU (approximately 24 million dairy cows) and does not yet account for the 5 and 20 million dairy cows in New-Zealand and Brazil, respectively, to name a few other important dairy markets. The dry cow segment holds the highest market share (>50%).

Mastitis is also relevant in other ruminant species such as dairy sheep and goats, a developing market seeking more tools to prevent and control this disease as well.

Besides the cost aspect, bovine mastitis has a substantial negative impact on animal welfare, comes with an enormous waste of milk not suited for consumption, and causes stress and extra labour for the dairy farmers and veterinarian.

Up to 70% of antimicrobials used on a dairy farm relate to this disease, which is becoming increasingly problematic in view of the emerging antimicrobial resistance crisis as now recognized by the WHO and the WOAH.

Technology

We engineered a novel and performant endolysin, NC5.

NC5 is:

• a chimeric fusion protein with lytic and antimicrobial properties

• a selected combination of enzymatically active domains (so called EADs),

which define the enzyme’s cleavage sites, and a cell wall-binding domain (so called CBD), which confers its bacterial specificity.

NC5 has the potential to:

• kill AMR streptococci, also in raw milk

• accelerate bacterial killing together with the narrow-spectrum, first choice

• antibiotic cloxacillin in mastitic raw cow’s milk derived from S. uberis infected cows

• kill intracellular streptococci

• eradicate streptococci-formed biofilms

Partnering

We are reaching out to partners who are interested in development and marketing of our novel engineered endolysin NC5.

We can offer expertise and facilities for in vitro and preclinical (in a mouse model) as well as clinical (in dairy cows) in vivo evaluation.

Contact

Sven ARNOUTS

+32 495 707 334

Sven.Arnouts@UGent.be

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