Experimental Phage Therapy in Treating Klebsiella pneumoniae -Mediated Liver Abscesses and Bacteremia in Mice

Abstract

Intragastric inoculation of mice with Klebsiella pneumoniae can cause liver abscesses, necrosis of liver tissues, and bacteremia. A newly isolated phage (NK5) with lytic activity for K. pneumoniae was used to treat K. pneumoniae infection in an intragastric model. Both intraperitoneal and intragastric administration of a single dose of NK5 lower than 2 ؋ 10 8 PFU at 30 min after K. pneumoniae infection was able to protect mice from death in a dose-dependent manner, but the efficacy achieved with a low dose of NK5 by intragastric treatment provided the more significant protection. Phage NK5 administered as late as 24 h after K. pneumoniae inoculation was still protective, while intraperitoneal treatment with phage was more efficient than intragastric treatment as a result of the dissemination of bacteria into the circulation at 24 h postinfection. Surveys of bacterial counts for mice treated with NK5 by the intraperitoneal route revealed that the bacteria were eliminated effectively from both blood and liver tissue. K. pneumoniae-induced liver injury, such as liver necrosis, as well as blood levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cytokine production, was significantly inhibited by NK5 treatment. These data suggest that a low dose of NK5 is a potential therapeutic agent for K. pneumoniae-induced liver infection.

Therapeutic potential of phages in autoimmune liver diseases

“…This confirms earlier data from experiments in mice 61 and in broilers in which dietary supplementation with phages increased liver weight 62.…”

Phages and Immunomodulation

“…Patterns of those cytokine differences were not dose related, indicating that phage treatment did not result in a strong immune response [42] (for normal ranges, see [43]). Tothova et al confirmed that phage therapy of urinary tract infections in mice attenuates the expression of proinflammatory cytokines [44], and the same effect was reported by Hung et al using a model of Klebsiella pneumoniae mediated liver abscess and bacteremia in mice [45]. In mice fed with murine norovirus, the inflammatory cytokine profiling showed increased levels of IL-1α, IL-1β, IL-2, IL-10, IL-12, IFN-γ and IFN-α.…”

Efficacy of Bacteriophage Therapy in Experimental Sepsis and Meningitis Caused by a Clone O25b:H4-ST131 Escherichia coli Strain Producing CTX-M-15

“…Though used for decades in Eastern Europe, successful phage therapy has been demonstrated only recently in experimental models (8,11,15,27,36,40,43,44). Because bacteriophage replicate at infection sites, efficacy may require just a single dose (23,40). Although phage-resistant mutants may be selected during treatment, they are often less virulent (8,23) and thus do not usually compromise treatment.…”

“…Because bacteriophage replicate at infection sites, efficacy may require just a single dose (23,40). Although phage-resistant mutants may be selected during treatment, they are often less virulent (8,23) and thus do not usually compromise treatment. In general, the specificity of phage infection ensures that the bulk of the body's microflora is unaffected (6,12).…”