Examining the efficacy of intravenous administration of predatory bacteria in rats

• Published in: Scientific reports Vol. 7; no. 1; pp. 1864 - 11
• Main Authors: Shatzkes, Kenneth, Singleton, Eric, Tang, Chi, Zuena, Michael, Shukla, Sean, Gupta, Shilpi, Dharani, Sonal, Rinaggio, Joseph, Kadouri, Daniel E., Connell, Nancy D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 38/77; 631/250/2499; 631/326/22; 631/326/2522; 631/61/51; 82/80; Animals; Bacteria; Bacterial diseases; Bacterial infections; Bacterial Infections - immunology; Bacterial Infections - microbiology; Bacterial Infections - pathology; Blood; Cytokines; Enzyme-Linked Immunosorbent Assay; Gram-negative bacteria; Histopathology; Host-Pathogen Interactions; Humanities and Social Sciences; Inflammation; Inoculation; Intravenous administration; Klebsiella pneumoniae; Male; Morbidity; multidisciplinary; Multidrug resistance; Predators; Rats; Rodents; Science; Science (multidisciplinary); Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02041-3

The proteobacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are obligate predators of Gram-negative bacteria, and have been proposed to be used to treat multidrug-resistant bacterial infections. The ability of predatory bacteria to reduce bacterial burden in vivo within the lungs of rats has been demonstrated, but it was unknown if predatory bacteria can attenuate systemic bacterial burden administered intravenously. In this study, we first assessed the safety of intravenous inoculation of predatory bacteria in rats. No rat morbidity or adverse histopathology of various organs due to predatory bacteria administration was observed. An increase in proinflammatory cytokines (TNFα and KC/GRO) was observed at two hours post-inoculation; however, cytokines returned to baseline levels by 18 hours. Furthermore, bacterial dissemination analysis demonstrated that predatory bacteria were efficiently cleared from the host by 20 days post-injection. To determine whether predatory bacteria could reduce bacterial burden in vivo , Klebsiella pneumoniae was injected into the tail veins of rats and followed with multiple doses of predatory bacteria over 16 or 24 hours. Predatory bacteria were unable to significantly reduce K. pneumoniae burden in the blood or prevent dissemination to other organs. The results suggest that predatory bacteria may not be effective for treatment of acute blood infections.