Measuring and modelling the response of Klebsiella pneumoniae KPC prey to Bdellovibrio bacteriovorus predation, in human serum and defined buffer

Abstract

In worldwide conditions of increasingly antibiotic-resistant hospital infections, it is important to research alternative therapies. Bdellovibrio bacteriovorus bacteria naturally prey on Gram-negative pathogens, including antibiotic-resistant strains and so B. bacteriovorus have been proposed as “living antibiotics” to combat antimicrobially-resistant pathogens. Predator-prey interactions are complex and can be altered by environmental components. To be effective B. bacteriovorus predation needs to work in human body fluids such as serum where predation dynamics may differ to that studied in laboratory media. Here we combine mathematical modelling and lab experimentation to investigate the predation of an important carbapenem-resistant human pathogen, Klebsiella pneumoniae, by B. bacteriovorus in human serum versus buffer. We show experimentally that B. bacteriovorus is able to reduce prey numbers in each environment, on different timescales. Our mathematical model captures the underlying dynamics of the experimentation, including an initial predation-delay at the predator-prey-serum interface. Our research shows differences between predation in buffer and serum and highlights both the potential and limitations of B. bacteriovorus acting therapeutically against K. pneumoniae in serum, informing future research into the medicinal behaviours and dosing of this living antibacterial.

Variation in genome content and predatory phenotypes between Bdellovibrio sp. NC01 isolated from soil and B. bacteriovorus type strain HD100

“…The predatory phenotypes observed during NC01 co-culture with E. coli ML35 may be the result of a mechanism specific to the prey, the predator, or a combination of the two. Other researchers have observed prey population recovery [66,67], and Shemesh and Jurkevitch demonstrated that recovery of Erwinia carotovora in co-cultures with Bdellovibrio isolated from soil was due to development of phenotypic resistance to predation. It is possible that E. coli ML35 uses a similar mechanism to develop resistance to predation by Bdellovibrio sp.…”

Insight into the Possible Use of the Predator Bdellovibrio bacteriovorus as a Probiotic

“…This is relevant considering that in vivo environments are more structurally complex than buffer systems. Baker and collaborators showed that there are differences between predation in buffer and serum, highlighting both the potential and limitations of B. bacteriovorus HD100 acting therapeutically against K. pneumoniae in serum, stimulating future research into the medicinal behaviors and dosing of this living antibacterial [93]. A comprehensive mathematical framework should consider interactions with the immune system, environmental conditions, and interactions with commensals in order to provide guidance for in vivo application and help researchers to design further dose schedules and therapeutic tests of predators.…”

Serralysin family metalloproteases protects Serratia marcescens from predation by the predatory bacteria Micavibrio aeruginosavorus

“…Elimination of flagella biosynthesis did not impact predation, as well, suggesting that flagellin does not serve as a predator-binding site. Although the motility of the prey might alter predator-prey encounter, the prey to predator ratio, as well as the small liquid volume used in the study is likely to allow sufficient random collisions of predator and prey, regardless of prey motility 26 , 27 . Koval and Hynes suggested that the paracrystalline protein surface layer (S-layer) of Aquaspirillum serpens, A. sinuosum and Aeromonas salmonicida provides protection from B. bacteriovorus predation 28 .…”