Measuring and modelling the response of Klebsiella pneumoniae KPC prey to Bdellovibrio bacteriovorus predation, in human serum and defined buffer
Measuring and modelling the response of Klebsiella pneumoniae KPC prey to Bdellovibrio bacteriovorus predation, in human serum and defined buffer
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DOI：
10.1038/s41598-017-08060-4
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发表时间：
2017-08-21
影响因子：
4.6
通讯作者：
Sockett, R. Elizabeth
中科院分区：
文献类型：
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作者：
Baker, Michelle;Negus, David;Sockett, R. Elizabeth
在全球范围内医院感染对抗生素耐药性日益增加的情况下，研究替代疗法非常重要。噬菌弧菌自然捕食革兰氏阴性病原体，包括抗生素耐药菌株，因此噬菌弧菌被提议作为“活抗生素”来对抗抗菌药物耐药病原体。捕食者与被捕食者之间的相互作用很复杂，并且可能会因环境因素而改变。为了有效，食菌芽孢杆菌的捕食需要在人体体液（例如血清）中起作用，其中捕食动力学可能与实验室介质中研究的不同。在这里，我们结合数学模型和实验室实验来研究食菌芽孢杆菌在人血清与缓冲液中捕食重要的耐碳青霉烯类人类病原体肺炎克雷伯菌的情况。我们通过实验证明，食菌芽孢杆菌能够在不同的时间尺度上减少每种环境中的猎物数量。我们的数学模型捕捉了实验的基本动态，包括捕食者-捕食血清界面处的初始捕食延迟。我们的研究显示了缓冲液和血清中捕食之间的差异，并强调了食菌芽孢杆菌对血清中肺炎克雷伯菌的治疗作用的潜力和局限性，为未来研究这种活细菌的药物行为和剂量提供信息。
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-preyserum 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.