Abstract
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.
Highlights
Bacterial infections are one of the major causes of morbidity and mortality in both man and economically important animals and impose a huge economical burden in terms of health care cost, lost manpower and contaminated food
P22sTsp showed slightly better agglutination than the Se155-4 antibody [37], which is specific to the O-antigen of Salmonella enterica serovar Typhimurium
In this study we showed that oral administration of Salmonellaspecific shortened tailspike protein (P22sTsp) significantly reduced Salmonella infection in chicks
Summary
Bacterial infections are one of the major causes of morbidity and mortality in both man and economically important animals and impose a huge economical burden in terms of health care cost, lost manpower and contaminated food. Due to the emergence of difficult-to-treat infections caused by antibiotic resistant bacteria, there is an urgent need for alternatives. Several other therapeutic approaches involving passive and active immunization, toxin binding agents, lytic bacteriophages, anti-bacterial peptides, phage lytic enzymes and probiotics have been used but they are far from replacing the antibiotic therapy approach [1,2,3,4,5,6,7,8,9]. Bacteriophages are host specific, selfreplicating, self limiting and virtually non-toxic. These characteristics have made lytic bacteriophages attractive therapeutic agents to combat bacterial infections. Despite their widely known therapeutic potential, bacteriophages have still not filled the gap of desperately needed alternatives to current antibacterial agents. Bacteriophage therapy is associated with drawbacks such as the possibility of showing reduced efficacy under anaerobic conditions in the gut due to bacterial regrowth [16], the emergence of phageresistant bacteria and the risk of horizontal gene transfer of virulence traits to the bacteria potentially rendering the target organism even more pathogenic [17,18,19]
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