Orally administered P22 phage tailspike protein reduces salmonella colonization in chickens: prospects of a novel therapy against bacterial infections

• Published in: PloS one 2010-11, Vol.5 (11), p.e13904-e13904
• Main Authors: Waseh, Shakeeba, Hanifi-Moghaddam, Pejman, Coleman, Russell, Masotti, Michael, Ryan, Shannon, Foss, Mary, MacKenzie, Roger, Henry, Matthew, Szymanski, Christine M, Tanha, Jamshid
• Format: Article
• Language: English
• Subjects: Administration, Oral; Agglutination; Agglutination - immunology; Animals; Antibiotic resistance; Antibiotics; Antibodies; Bacteria; Bacterial diseases; Bacterial infections; Bacterial Translocation - drug effects; Bacteriophage P22 - metabolism; Campylobacter jejuni; Cecum - drug effects; Cecum - microbiology; Chickens; Chymotrypsin; Colonization; Computational fluid dynamics; Contamination; Councils; Decolonization; Digestive tract; Economic importance; Enzymes; Food contamination & poisoning; Gastrointestinal system; Gastrointestinal tract; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - microbiology; Glycoside Hydrolases; Health aspects; Hydrolases; Immunoglobulins; In vivo methods and tests; Infection; Infections; Infectious Diseases/Bacterial Infections; Inflammatory bowel disease; Lipopolysaccharides; Liver - drug effects; Liver - microbiology; Microbial drug resistance; Microbiology; Morbidity; Mortality; Motility; Oral administration; Organs; Pathogens; Pepsin; Pepsin A; Peptide Hydrolases - metabolism; Phages; Podoviridae; Poultry; Proteinase; Proteins; Proteolysis; Public Health and Epidemiology/Infectious Diseases; Salmonella; Salmonella enterica; Salmonella Infections, Animal - drug therapy; Salmonella Infections, Animal - microbiology; Salmonella Typhimurium; Salmonella typhimurium - growth & development; Salmonella typhimurium - immunology; Salmonella typhimurium - virology; Spleen - drug effects; Spleen - microbiology; Tailspike protein; Therapy; Trypsin; Tumor necrosis factor-TNF; Viral Tail Proteins - administration & dosage; Viral Tail Proteins - immunology; Viral Tail Proteins - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013904

One of the major causes of morbidity and mortality in man and economically important animals is bacterial infections of the gastrointestinal (GI) tract. The emergence of difficult-to-treat infections, primarily caused by antibiotic resistant bacteria, demands for alternatives to antibiotic therapy. Currently, one of the emerging therapeutic alternatives is the use of lytic bacteriophages. In an effort to exploit the target specificity and therapeutic potential of bacteriophages, we examined the utility of bacteriophage tailspike proteins (Tsps). Among the best-characterized Tsps is that from the Podoviridae P22 bacteriophage, which recognizes the lipopolysaccharides of Salmonella enterica serovar Typhimurium. In this study, we utilized a truncated, functionally equivalent version of the P22 tailspike protein, P22sTsp, as a prototype to demonstrate the therapeutic potential of Tsps in the GI tract of chickens. Bacterial agglutination assays showed that P22sTsp was capable of agglutinating S. Typhimurium at levels similar to antibodies and incubating the Tsp with chicken GI fluids showed no proteolytic activity against the Tsp. Testing P22sTsp against the three major GI proteases showed that P22sTsp was resistant to trypsin and partially to chymotrypsin, but sensitive to pepsin. However, in formulated form for oral administration, P22sTsp was resistant to all three proteases. When administered orally to chickens, P22sTsp significantly reduced Salmonella colonization in the gut and its further penetration into internal organs. In in vitro assays, P22sTsp effectively retarded Salmonella motility, a factor implicated in bacterial colonization and invasion, suggesting that the in vivo decolonization ability of P22sTsp may, at least in part, be due to its ability to interfere with motility… Our findings show promise in terms of opening novel Tsp-based oral therapeutic approaches against bacterial infections in production animals and potentially in humans.