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Project
Phage-encoded endolysins as a new control measure against tegen methicillin resistant Staphylococcus aureus in pigs (IWT464)
Methicillin-resistant Staphylococcus aureus (MRSA) are multi-resistant germs that cause many problems in human medicine. Recently, a new reservoir of MRSA found in animals. This reservoir was first detected in pigs, but from a variety of Belgian and international studies indicate that other species are colonised.
MRSA infections were rarely described in animal species other than horses.
In the case of bovines a number of cases of clinical mastitis were recently found (P. Butaye, unpublished data). This animal reservoir consists of one specific type, the "animal-related" type, which can be divided in a number of related subtypes. This "animal-related" type is also found in farmers. MRSA infections were also observed dogs; these were mainly of human origin.
In humans, there are two types, namely the hospital connected HA-MRSA and the MRSA associated with the Community (CA-MRSA). The germs are the cause of serious infections that are often fatal. HA-MRSA infections were rarely found in horses and dogs, but these were caused by human contamination during surgery.
Animal associated MRSA are a potential danger to both the animal health and public health. These animal-associated MRSA complicate in the first place the diagnosis, because they are difficult to distinguish the more dangerous human HA-MRSA (MRSA isolation and characterisation) and, secondly, because the virulence of bacteria may vary. In addition, animal associated MRSA bacteria can acquire virulence traits situated on mobile genetic elements, and thus become highly pathogenic strains. That is why this problem must be treated proactively. Antibiotic therapy of animals is difficult, given the broad resistance, and is not appropriate, because of the likelihood that the germs may become multi-resistant. Other measures, such as hygiene measures do not work directly on animals, and possibly have only a partial effect.
Since the MRSA found in animals and is very clonal and because fagen is usually a very strict host specificity, phage-encoded endolysins are a very suitable means to control specific MRSA in the animal reservoir. Since S. aureus and thus also MRSA colonize epithelial tissues such as skin and nasal epithelium nasal these phage enzymes will be applied on the skin or in the nose.
The purpose of this project is to make pigs free of MRSA, or at least to achieve a substantial reduction of the colonization, in order to prevent or decrease the chances of infection of humans. To achieve this, phage endolysines will overproduced in Escherichia coli and Pichia pastoris and purified for use in the in vivo treatment of experimental animals.
The development of the new bactericidal treatment is therefore based on enzymes produced by bacteriophages and will be used to obtain animals free of MRSA, or to obtain a substantial reduction. The specific objectives of this project will include the following :
* Isolate and overproduce a representative set of phage-encoded lysines active against the specific MRSA clones that are present in animals, in particular pigs
* Characterization of the host specificity of these enzymes.
* Study on the efficiency, in vitro and in animal models of the bactericidal activity of these phage enzymes.
* To test methods for the administration of the phage enzyme preparation in the nose and on the skin in pigs.
* The testing of the effectiveness of the faag enzyme treatment for the elimination of MRSA colonisation in pigs.
MRSA infections were rarely described in animal species other than horses.
In the case of bovines a number of cases of clinical mastitis were recently found (P. Butaye, unpublished data). This animal reservoir consists of one specific type, the "animal-related" type, which can be divided in a number of related subtypes. This "animal-related" type is also found in farmers. MRSA infections were also observed dogs; these were mainly of human origin.
In humans, there are two types, namely the hospital connected HA-MRSA and the MRSA associated with the Community (CA-MRSA). The germs are the cause of serious infections that are often fatal. HA-MRSA infections were rarely found in horses and dogs, but these were caused by human contamination during surgery.
Animal associated MRSA are a potential danger to both the animal health and public health. These animal-associated MRSA complicate in the first place the diagnosis, because they are difficult to distinguish the more dangerous human HA-MRSA (MRSA isolation and characterisation) and, secondly, because the virulence of bacteria may vary. In addition, animal associated MRSA bacteria can acquire virulence traits situated on mobile genetic elements, and thus become highly pathogenic strains. That is why this problem must be treated proactively. Antibiotic therapy of animals is difficult, given the broad resistance, and is not appropriate, because of the likelihood that the germs may become multi-resistant. Other measures, such as hygiene measures do not work directly on animals, and possibly have only a partial effect.
Since the MRSA found in animals and is very clonal and because fagen is usually a very strict host specificity, phage-encoded endolysins are a very suitable means to control specific MRSA in the animal reservoir. Since S. aureus and thus also MRSA colonize epithelial tissues such as skin and nasal epithelium nasal these phage enzymes will be applied on the skin or in the nose.
The purpose of this project is to make pigs free of MRSA, or at least to achieve a substantial reduction of the colonization, in order to prevent or decrease the chances of infection of humans. To achieve this, phage endolysines will overproduced in Escherichia coli and Pichia pastoris and purified for use in the in vivo treatment of experimental animals.
The development of the new bactericidal treatment is therefore based on enzymes produced by bacteriophages and will be used to obtain animals free of MRSA, or to obtain a substantial reduction. The specific objectives of this project will include the following :
* Isolate and overproduce a representative set of phage-encoded lysines active against the specific MRSA clones that are present in animals, in particular pigs
* Characterization of the host specificity of these enzymes.
* Study on the efficiency, in vitro and in animal models of the bactericidal activity of these phage enzymes.
* To test methods for the administration of the phage enzyme preparation in the nose and on the skin in pigs.
* The testing of the effectiveness of the faag enzyme treatment for the elimination of MRSA colonisation in pigs.
Date:1 Dec 2009 → 30 Nov 2013
Keywords:Bacteriophage, MRSA, Endolysin, Staphylococcus aureus, Biology, pig
Disciplines:Basic sciences, Biological sciences