Abstract

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as Bdellovibrio bacteriovorus, is among the novel approaches being considered as possible therapeutics for antibiotic resistant and/or unidentified bacterial infections. Previous studies have examined the feasibility of using predatory bacteria to reduce colony-forming units (CFUs) in the lungs of rats exposed to lethal doses of Klebsiella pneumoniae; here we apply the approach to the Tier 1 select agent Yersinia pestis, and show that three doses of B. bacteriovorus introduced every six hours reduces the number of CFUs of Y. pestis in the lungs of inoculated mice by 86% after 24 h of infection. These experiments further demonstrate that predatory bacteria may serve to combat Gram negative bacterial infections, including those considered potential bioweapon agents, in the future.

Highlights

  • The United Nations General Assembly met in 2016 to discuss the crisis of antimicrobial resistance (AMR), in the face of predictions that if AMR continues to spread at current rates, there would be an estimated 10 million deaths globally by 2050 [1]

  • Bacteriophages have proven to be one possible option and are already in use in several countries [5,6,7]. Another approach is the use of predatory bacteria, a group of Gram negative proteobacteria, including Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus

  • The predatory bacterial strain used in the study was Bdellovibrio bacteriovorus 109J (ATCC 15143)

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Summary

Introduction

The United Nations General Assembly met in 2016 to discuss the crisis of antimicrobial resistance (AMR), in the face of predictions that if AMR continues to spread at current rates, there would be an estimated 10 million deaths globally by 2050 [1]. True to form, recent strains of clinical K. pneumoniae have demonstrated colistin resistance, injecting a new level of alarm among infectious disease researchers, clinicians and public health practitioners [4]. Bacteriophages have proven to be one possible option and are already in use in several countries [5,6,7] Another approach is the use of predatory bacteria, a group of Gram negative proteobacteria, including Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus. These species are obligate predators of Gram-negative bacteria, and have been proposed to be used to treat multidrug-resistant bacterial infections [8,9]. Previous studies from this laboratory with rat and mouse models have shown that the predator bacteria, administered at high

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