Loessner Holger, Schlattmeier Insea, Anders-Maurer Marie, Bekeredjian-Ding Isabelle, Rohde Christine, Wittmann Johannes, Pokalyuk Cornelia, Krut Oleg, Kamp Christel
Paul-Ehrlich-Institut, 63225 Langen, Germany.
Goethe University Frankfurt, 60323 Frankfurt, Germany.
Antibiotics (Basel). 2020 Jul 14;9(7):408. doi: 10.3390/antibiotics9070408.
The specific temporal evolution of bacterial and phage population sizes, in particular bacterial depletion and the emergence of a resistant bacterial population, can be seen as a that depends on the manifold interactions of the specific phage-host pair during the course of infection. We have elaborated such a kinetic fingerprint for a human urinary tract isolate and its phage vB_KpnP_Lessing by a modeling approach based on data from co-culture. We found a faster depletion of the initially sensitive bacterial population than expected from simple mass action kinetics. A possible explanation for the rapid decline of the bacterial population is a synergistic interaction of phages which can be a favorable feature for phage therapies. In addition to this interaction characteristic, analysis of the kinetic fingerprint of this bacteria and phage combination revealed several relevant aspects of their population dynamics: A reduction of the bacterial concentration can be achieved only at high multiplicity of infection whereas bacterial extinction is hardly accomplished. Furthermore the binding affinity of the phage to bacteria is identified as one of the most crucial parameters for the reduction of the bacterial population size. Thus, kinetic fingerprinting can be used to infer phage-host interactions and to explore emergent dynamics which facilitates a rational design of phage therapies.
细菌和噬菌体种群大小的特定时间演变，特别是细菌数量的减少和抗性细菌种群的出现，可以被视为一种取决于感染过程中特定噬菌体 - 宿主对多种相互作用的情况。我们通过基于共培养数据的建模方法，为一种人类尿道分离菌株及其噬菌体vB_KpnP_Lessing阐述了这样一种动力学特征。我们发现，最初敏感的细菌种群数量的减少比简单质量作用动力学预期的要快。细菌种群迅速减少的一个可能解释是噬菌体的协同相互作用，这对于噬菌体疗法来说可能是一个有利特征。除了这种相互作用特征外，对这种细菌和噬菌体组合的动力学特征分析还揭示了它们种群动态的几个相关方面：只有在高感染复数时才能实现细菌浓度的降低，而细菌灭绝几乎无法完成。此外，噬菌体与细菌的结合亲和力被确定为减少细菌种群大小的最关键参数之一。因此，动力学特征分析可用于推断噬菌体 - 宿主相互作用，并探索涌现动态，这有助于合理设计噬菌体疗法。
