Journal of Theoretical Biology最新文献_第4页

A model of predation and survival in a system of three interacting species 一个由三个相互作用的物种组成的捕食和生存系统的模型。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-12-09 DOI: 10.1016/j.jtbi.2025.112330

Anca Rǎdulescu , Richard Halpern , Drew Kozlowski

The study of intra-guild interactions in an ecosystem is an active and impactful direction of inquiry. This is true in particular for fragile systems in which even small perturbations of their functional parameters can produce dramatic effects like species endangerment or extinction, leading the system to enter an unsustainable regime and eventually collapse. In this context, it is important to understand which factors can lead to such effects and for which systems, so that one can act proactively and timely to prevent them. We built and studied a mathematical model that captures the natural interactions in an intra-guild, three species system (i.e., in which two species are predators of the third, but such that one of the predators also consumes the other). The nonlinear components of the model were documented on existing literature and assembled as a system of Lotka-Volterra ordinary differential equations. Our analytical computations and numerical explorations revealed sequences of transcritical and Hopf bifurcations underlying counterintuitive transitions of the system into regions of vulnerability to external noise. We conclude that, in order to avoid extinction, one needs to rigorously prescribe a well-documented, prediction-based approach to population control.

对生态系统中同业互动的研究是一个积极而有影响力的研究方向。对于脆弱的系统来说尤其如此，在这些系统中，即使对其功能参数的微小扰动也会产生巨大的影响，如物种濒危或灭绝，导致系统进入不可持续的状态并最终崩溃。在这种情况下，重要的是要了解哪些因素会导致这样的影响，以及对哪些系统造成这样的影响，以便人们能够主动及时地采取行动来预防它们。我们建立并研究了一个数学模型，该模型捕捉了一个行内三物种系统中的自然相互作用（即两个物种是第三个物种的捕食者，但其中一个捕食者也会消耗另一个物种）。该模型的非线性成分记录在现有文献中，并组装为Lotka-Volterra常微分方程系统。我们的分析计算和数值探索揭示了跨临界和Hopf分岔序列，这些分岔是系统进入易受外部噪声影响区域的反直觉转变的基础。我们的结论是，为了避免灭绝，人们需要严格规定一种有充分证据的、基于预测的人口控制方法。

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引用次数: 0

Antibody escape of SARS-CoV-2 variants of concern on receptor-binding domain: A computational approach 受体结合域关注的SARS-CoV-2变体的抗体逃逸：一种计算方法

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-12-06 DOI: 10.1016/j.jtbi.2025.112345

Dac-Nhan Nguyen , Quoc-Thai Nguyen , Thoai-My Dang , Phuong-Uyen Tran-Thi , Viet-Hung Tran , Minh-Tri Le , Lam-Truong Tuong , Van-Thanh Tran , Phuong Nguyen Hoai Huynh , Khac-Minh Thai

The receptor-binding domain (RBD) of the spike protein is a critical functional component responsible for binding between the SARS-CoV-2 and the ACE2 receptor, as well as monoclonal antibodies. This research focuses on evaluating the ability of SARS-CoV-2 variants to reduce or evade neutralizing antibody responses. The RBD structures of wild type, Delta, and Omicron structures along with nine RBD-directed antibodies downloaded from the Protein Data Bank were subjected to docking simulations via the HADDOCK 2.4 server to calculate Haddock score, binding affinity (ΔG) and dissociation constant (K_d). The resulting complexes underwent molecular dynamics simulations for 100 ns using GROMACS, and the binding free energy was calculated using gmx_MMPBSA. The findings indicated that the L452R and T478K mutations in Delta, as well as the K417N, E484A, S477N, and Q493R mutations in Omicron, were predicted to be pivotal factors in the interaction with antibodies. Omicron exhibited a greater potential for immune evasion compared to Delta. Notably, the Sotrovimab antibody demonstrated robust interactions with both variants. Etesevimab exhibited strong binding with Delta but displayed a weaker connection with Omicron. Therefore, Sotrovimab and Etesevimab remain promising candidates for in vitro and in vivo testing against SARS-CoV-2 variants.

刺突蛋白的受体结合域（RBD）是负责SARS-CoV-2与ACE2受体以及单克隆抗体结合的关键功能成分。本研究的重点是评估SARS-CoV-2变体减少或逃避中和抗体反应的能力。将野生型、Delta和Omicron结构的RBD结构与从蛋白质数据库下载的9种RBD定向抗体通过HADDOCK 2.4服务器进行对接模拟，计算HADDOCK评分、结合亲和力（ΔG）和解离常数（Kd）。用GROMACS对得到的配合物进行了100 ns的分子动力学模拟，并用gmx_MMPBSA计算了结合自由能。结果表明，Delta基因的L452R和T478K突变，以及Omicron基因的K417N、E484A、S477N和Q493R突变预计是与抗体相互作用的关键因素。与德尔塔相比，欧米克隆表现出更大的免疫逃避潜力。值得注意的是，Sotrovimab抗体与这两种变体表现出强大的相互作用。Etesevimab与Delta结合较强，与Omicron结合较弱。因此，Sotrovimab和Etesevimab仍然是针对SARS-CoV-2变体的体内和体内测试的有希望的候选药物。

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引用次数: 0

Dispersal in multi-patch metapopulations: The impact of patch number and network topology 多斑块元种群的分散：斑块数和网络拓扑的影响。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-12-02 DOI: 10.1016/j.jtbi.2025.112331

Juan Segura , Marcos Marvá , Daniel Franco

Habitat fragmentation is a leading cause of biodiversity loss, and efforts to enhance connectivity through, for example, biological corridors are a common conservation strategy to mitigate it. However, understanding the effects of dispersal variation on the total biomass of spatially structured populations is still far from being well understood. For the simplest situation, i.e., a population occupying a habitat divided into two patches, recent studies have shown that there are only four possible response scenarios to increased connectivity in discrete- and continuous-time models under Beverton-Holt and logistic local dynamics, respectively. This paper explores whether the number of patches in a metapopulation influences the number of response scenarios to increased dispersal. We will show that for given local dynamics the number of possible response scenarios significantly increases when the number of patches increases from two to three. Moreover, the paper revisits the problem of how network topology affects total biomass dynamics for low dispersal rates. We will show that the previous claim that bidirectional connectivity always increases biomass at low dispersal rates when connecting sources is false. Indeed, we will prove that transiting from a chain topology to a ring topology can either increase or decrease the total biomass for low dispersal rates if one considers more realistic production functions or if the probability of using a concrete path is not the same in the whole metapopulation.

栖息地破碎化是生物多样性丧失的主要原因，通过生物走廊等方式加强连通性是缓解这一问题的常见保护策略。然而，对种群扩散变化对空间结构种群总生物量的影响还远远没有得到很好的理解。最近的研究表明，对于最简单的情况，即种群占据的栖息地分为两个斑块，在贝弗顿-霍尔特和logistic局部动力学的离散时间和连续时间模型中，分别只有四种可能的响应情景。本文探讨了元种群中斑块的数量是否会影响对增加分散的响应情景的数量。我们将表明，对于给定的局部动力学，当补丁数量从两个增加到三个时，可能的响应场景的数量显着增加。此外，本文重新审视了网络拓扑结构如何影响低扩散速率下的总生物量动态。我们将证明，当连接源时，以前的双向连接总是在低分散速率下增加生物量的说法是错误的。事实上，我们将证明，如果考虑更现实的生产函数，或者在整个元种群中使用具体路径的概率不相同，从链状拓扑过渡到环状拓扑可以增加或减少低扩散率下的总生物量。

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引用次数: 0

Demographic consequences of the loss of mating opportunities in a two-species reproductive interference system 两种生殖干扰系统中交配机会丧失的人口统计学后果。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-29 DOI: 10.1016/j.jtbi.2025.112332

Yusuke Ikegawa , Chihiro Himuro , Atsushi Honma

Reproductive interference (RI) includes any negative effect on reproductive success of females that is induced by interspecific sexual interactions. Although previous population dynamic models of RI have focused on population-level processes (e.g., changes in population size), individual-level processes (e.g., search and courtship by males and subsequent choice by females) have been largely overlooked. In this study, we constructed a discrete-time population dynamic model comprising two species, assuming iterative courtship and mating within each reproductive time period (i.e., individual-level process) and subsequent population dynamics (i.e., population-level process). We assumed that if males (or females) have wide acceptance range to their counterparts, correct courtship (or mating) to conspecifics and incorrect courtship to heterospecifics would increase simultaneously. We also assumed that two species have different demographics (species 1 with higher reproduction and mortality, species 2 with lower reproduction and mortality). We showed that intermediate acceptance range of females mitigated the negative effect of courtship from heterospecific males on mating success. However, the initially more abundant species 1 can be outcompeted by the initially less abundant species 2. This is because the net negative effect of losing mating opportunities due to RI was greater for species 1 with higher mortality than for species 2 with lower mortality. Overall, the results of reproductive success, which are derived only from individual-level processes, are not always consistent with the demographic consequences, which are derived from both individual- and population-level processes. We propose that analyzing the RI system by considering both individual- and population-level processes is necessary.

生殖干扰（Reproductive interference， RI）是指由种间性互动引起的对雌性生殖成功的负面影响。虽然以前的种群动态模型集中在种群水平的过程（例如，种群规模的变化），但个体水平的过程（例如，雄性的寻找和求爱以及雌性随后的选择）在很大程度上被忽视了。在本研究中，我们构建了一个由两个物种组成的离散时间种群动态模型，该模型假设每个繁殖周期内的求偶和交配迭代过程（即个体水平过程）和随后的种群动态过程（即种群水平过程）。我们认为，如果雄性（或雌性）对异性的接受范围较宽，那么对同种异性的正确求偶（或交配）和对异种异性的不正确求偶会同时增加。我们还假设两个物种具有不同的人口统计学特征（物种1的繁殖率和死亡率较高，物种2的繁殖率和死亡率较低）。研究表明，雌性的中间接受范围减轻了异性雄性求偶对交配成功的负面影响。然而，最初丰度较高的物种1可能会被最初丰度较低的物种2打败。这是因为由于RI而失去交配机会的净负面影响对死亡率较高的物种1比死亡率较低的物种2更大。总的来说，生殖成功的结果只来自个人一级的过程，并不总是与人口的结果一致，而人口的结果则来自个人和人口一级的过程。我们建议在分析国际扶轮系统时，必须同时考虑个人与族群层面的过程。

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引用次数: 0

Immune responses may make HIV-1 therapeutic interfering particles less effective 免疫反应可能使HIV-1治疗干扰颗粒效果降低。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-29 DOI: 10.1016/j.jtbi.2025.112317

Griffin Kutler Dodd, Rob J. de Boer

The current standard treatment for HIV-1 infection is antiretroviral therapy, which effectively suppresses viral replication but requires a lifelong drug regimen. An alternative treatment approach is a single injection of a modified version of the HIV-1 virus, termed a therapeutic interfering particle (TIP), that lacks replication machinery and suppresses the wild-type virus by competing for viral proteins. Here, we derive a novel ordinary differential equation model of TIP dynamics. We confirm results from previous models that TIPs can reduce viral load when doubly infected cells produce at least as many virus particles as singly infected cells. By deriving the basic reproduction number

R_{0}^{T}

of a TIP, we predict that concurrent antiretroviral therapy should make it more difficult for a TIP to persist in a host. Adding an immune response to our model reveals that even a moderate immune response against virally infected cells drastically decreases the range of parameter values for which therapy is effective. Together, these results show that the success of TIPs depend on the properties of the wild-type virus and even more strongly on the immune response, which makes it hard to predict therapeutic success.

目前治疗HIV-1感染的标准疗法是抗逆转录病毒疗法，这种疗法能有效抑制病毒复制，但需要终生服药。另一种治疗方法是单次注射HIV-1病毒的修饰版本，称为治疗干扰粒子（TIP），它缺乏复制机制，通过竞争病毒蛋白来抑制野生型病毒。本文推导了一种新型的TIP动力学常微分方程模型。我们证实了先前模型的结果，即当双重感染的细胞产生至少与单一感染的细胞一样多的病毒颗粒时，TIPs可以减少病毒载量。通过推导TIP的基本繁殖数R0T，我们预测同时进行抗逆转录病毒治疗会使TIP更难以在宿主中持续存在。在我们的模型中加入免疫反应表明，即使是针对病毒感染细胞的适度免疫反应也会大大降低治疗有效的参数值范围。总之，这些结果表明，TIPs的成功取决于野生型病毒的特性，甚至更强烈地取决于免疫反应，这使得很难预测治疗成功。

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引用次数: 0

Mechanisms of reentry arrhythmia termination with ephaptic coupling and gap junctional coupling 再入性心律失常终止与心动偶联和间隙连接偶联的机制。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-18 DOI: 10.1016/j.jtbi.2025.112308

Ning Wei , Joyce Lin

Cardiac cells communicate electrically to coordinate heart contractions and pump blood. Gap junctions in the intercalated discs (ID) between myocytes form low-resistance pathways that facilitate electrical propagation. Traditionally, gap junctional coupling is considered the primary mechanism for cell communication, but experimental studies show that conduction can persist even with impaired gap junctions. For example, in gap junction-deficient rats, the heart still shows slow, discontinuous signal propagation, suggesting the existence of other communication mechanisms. One such mechanism is ephaptic coupling (EpC), an electrical field effect in the ID that maintains conduction even in the absence of gap junctions. EpC has been explored experimentally and numerically, especially in altered ID under normal and diseased conditions. However, a lack of direct evidence emphasizes the need to study its physiological role in the heart. Some research indicates that EpC can increase conduction velocity (CV) and reduce conduction failure, but its effects on cardiac arrhythmias are not well understood. Our study focuses on reentry arrhythmia, where rapid, irregular heartbeats can lead to cardiac arrest. Previous modeling work suggests that strong EpC can terminate reentry in ischemic hearts, though the mechanism remains unclear. We aim to investigate the mechanisms underlying reentry termination across different levels of EpC and gap junctional coupling using a two-dimensional discrete bidomain model with EpC. Our results identify two mechanisms: (1) Strong EpC terminates reentry through self-attenuation, driven by inactivation of fast sodium currents and (2) moderate EpC terminates reentry through self-collision, influenced by increased CV and anisotropy. A boundary where termination does not occur is also observed.

心脏细胞通过电通信来协调心脏收缩和泵血。肌细胞间的间隙连接形成低阻通路，促进电传播。传统上，缝隙连接耦合被认为是细胞通讯的主要机制，但实验研究表明，即使缝隙连接受损，传导也可以持续。例如，在间隙连接缺陷大鼠中，心脏仍然表现出缓慢、不连续的信号传播，这表明存在其他通信机制。其中一种机制是触觉耦合（ephaptic coupling, EpC），这是一种电场效应，即使在没有间隙连接的情况下，也能保持传导。EpC已经在实验和数值上进行了探索，特别是在正常和病变条件下改变的ID。然而，缺乏直接证据强调了研究其在心脏中的生理作用的必要性。一些研究表明，EpC可以提高传导速度（CV），减少传导衰竭，但其对心律失常的影响尚不清楚。我们的研究重点是再入性心律失常，其中快速，不规则的心跳可导致心脏骤停。先前的建模工作表明，强EpC可以终止缺血心脏的再入，尽管机制尚不清楚。我们的目的是利用二维离散双域模型研究不同EpC水平和间隙连接耦合的再入终止机制。我们的研究结果确定了两种机制：(1)强EpC通过自衰减终止再入，由快速钠电流失活驱动；(2)中等EpC通过自碰撞终止再入，受CV和各向异性增加的影响。还观察到不发生终止的边界。

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引用次数: 0

Multiscale analysis of electrically stimulated vascularised tumours 电刺激血管肿瘤的多尺度分析。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-17 DOI: 10.1016/j.jtbi.2025.112307

Zita Borbála Fülöp, Raimondo Penta

Electroporation-based therapies such as electrochemotherapy (ECT) hold a great promise for improving cancer treatments. While highly effective for superficial tumours, its application for deep-seated malignancies is challenged by complex microstructural properties, and current models often lack a multiscale theoretical framework to capture those phenomena. Here we develop and solve a novel system of coupled partial differential equations of Darcy-Laplace type obtained by applying the asymptotic homogenisation technique. We study the tumour response stimulated by an electric field. We derive effective macroscale equations for the pressure, velocity, and electric potential, whilst incorporating both hydraulic and electric microscale tissue heterogeneities. Our coupled multiscale approach bridges the gap between the tumour microstructure and macroscale dynamics, offering a more comprehensive understanding of how tumour size, morphology, and hydraulic-electrical interactions influence interstitial flow. We present a parametric analysis of the hydraulic conductivity tensor and macroscale numerical simulation results for pressure and velocity fields, highlighting the role of the electric field in modulating fluid flow. Our findings provide meaningful insights towards advancing ECT protocols.

以电穿孔为基础的疗法，如电疗（ECT），对改善癌症治疗有很大的希望。虽然对浅表肿瘤非常有效，但其在深层恶性肿瘤中的应用受到复杂微观结构特性的挑战，目前的模型往往缺乏多尺度理论框架来捕捉这些现象。本文利用渐近均匀化技术，建立并求解了一类新的达西-拉普拉斯型耦合偏微分方程组。我们研究电场刺激下肿瘤的反应。我们推导了有效的宏观尺度的压力、速度和电势方程，同时结合了水力和电微观尺度的组织异质性。我们的耦合多尺度方法弥合了肿瘤微观结构和宏观尺度动力学之间的差距，提供了对肿瘤大小、形态和液压-电相互作用如何影响间隙流动的更全面的理解。我们给出了水力传导张量的参数化分析和压力场和速度场的宏观数值模拟结果，强调了电场在调节流体流动中的作用。我们的发现为推进电痉挛疗法提供了有意义的见解。

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引用次数: 0

Integrating community level transmission geographical networks into a dynamical system for better epidemic control 将社区层面的传播地理网络整合为动态系统，以更好地控制疫情。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-15 DOI: 10.1016/j.jtbi.2025.112319

Arni S.R. Srinivasa Rao , Steven G. Krantz , John P. Barile

Despite the widespread use of deterministic models in understanding and controlling epidemics, they are often criticized for their inability to provide timely practical solutions during rapid spread. Similarly, conventional stochastic and statistical models also have limitations in providing time-sensitive solutions. These models are useful for implementing policy measures when there is enough time to make changes. In this article, we propose a novel approach to address these limitations by introducing a graphical network model with time-sensitive data blending to enhance deterministic epidemic models like the SIR model. This innovative approach could be valuable for rapidly spreading epidemics, providing timely model-based solutions to control their spread. For the first time, this article introduces higher-dimensional transmission rate functions in the literature and methods to obtain such functions.

AMS MSC 2020 classifications: 92D30; 62P10; 65T60.

尽管确定性模型被广泛用于了解和控制流行病，但它们经常因无法在快速传播期间提供及时的实际解决方案而受到批评。同样，传统的随机和统计模型在提供时间敏感的解决方案方面也有局限性。当有足够的时间进行更改时，这些模型对于实施政策措施非常有用。在本文中，我们提出了一种新的方法来解决这些限制，通过引入具有时间敏感数据混合的图形网络模型来增强确定性流行病模型，如SIR模型。这种创新的方法对于迅速传播的流行病可能很有价值，可以提供及时的基于模型的解决方案来控制其传播。本文首次介绍了文献中已有的高维传输速率函数，以及高维传输速率函数的获取方法。AMS MSC 2020分类：92D30；62 p10;65诸如 T60。

引用次数: 0

Reducing size bias in epidemic network modelling 减少流行病网络模型中的大小偏差。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-15 DOI: 10.1016/j.jtbi.2025.112314

Neha Bansal, Katerina Kaouri, Thomas E. Woolley

Epidemiological models can inform policymaking on disease control strategies, and these models often rely on sampled contact networks. The Random Walk (RW) sampling algorithm, commonly used for network sampling, produces size-biased samples that over-represent highly connected individuals, leading to biased estimates of disease spread. The Metropolis-Hastings Random Walk (MHRW) addresses this by providing samples representative of the underlying network’s connectivity distribution. We compare MHRW and RW in reducing size bias across four network types: Erdös-Rényi (ER), Small-world (SW), Negative-binomial (NB), and Scale-free (SF). We simulate disease spread using a stochastic Susceptible-Infected-Recovered (SIR) framework. RW tends to overestimate infections (by 25 % in ER, SW, NB) and secondary infections (by 25 % in ER, SW and 80 % in NB), and underestimate time-to-infection in NB networks. MHRW reduces the size bias, except on SF networks, where both algorithms provide non-representative samples and highly variable estimates. We find that RW is appropriate for fast-spreading, high-mortality epidemics in homogeneous or moderately random networks (ER, SW). In contrast, MHRW is better suited for slower and low-severity epidemics and can be effective in both homogeneous and heterogeneous networks (ER, SW, NB). However, MHRW is computationally expensive and less accurate when duplicate nodes are removed. We also analyse real-world data from cattle movement and human contact networks; MHRW generates disease spread estimates closer to the underlying network than RW. Our findings guide the selection of sampling algorithms based on network structure and epidemic characteristics, enhancing the reliability of disease modelling for policymaking.

流行病学模型可以为疾病控制战略的决策提供信息，而这些模型往往依赖于抽样接触网络。随机漫步（RW）抽样算法通常用于网络抽样，它产生的样本有大小偏差，过度代表高度联系的个体，导致对疾病传播的估计有偏差。Metropolis-Hastings Random Walk （MHRW）通过提供代表底层网络连接分布的样本来解决这个问题。我们比较了MHRW和RW在四种网络类型（Erdös-Rényi （ER）、小世界（SW）、负二项（NB）和无标度（SF））中减少尺寸偏差的效果。我们使用随机易感-感染-恢复（SIR）框架模拟疾病传播。RW倾向于高估感染（在ER、SW、NB中为25%）和继发性感染（在ER、SW中为25%，在NB中为80%），并低估NB网络中的感染时间。除了SF网络，MHRW减少了大小偏差，其中两种算法都提供了非代表性样本和高度可变的估计。我们发现RW适用于同质或中等随机网络中快速传播、高死亡率的流行病（ER， SW）。相比之下，MHRW更适合于较慢和低严重程度的流行病，并且可以在同质和异质网络中有效（ER、SW、NB）。然而，MHRW的计算成本很高，并且在删除重复节点时准确性较低。我们还分析了来自牛的运动和人类接触网络的真实数据；MHRW产生的疾病传播估计值比RW更接近基础网络。我们的研究结果指导了基于网络结构和流行病特征的抽样算法的选择，提高了疾病建模为政策制定提供的可靠性。

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引用次数: 0

Drug mode of action and resource constraints modulate antimicrobial resistance evolution 药物作用模式和资源限制调节抗菌素耐药性的演变。

IF 2 4区数学 Q2 BIOLOGY

Journal of Theoretical Biology

Pub Date : 2025-11-14 DOI: 10.1016/j.jtbi.2025.112316

Oscar Delaney, Christopher~R.~P. Brown, Andrew~D. Letten, Jan Engelstäder

An increasingly important goal in the design of antimicrobial treatment regimens is to minimise the probability of resistance evolving, without harming individual patients’ outcomes. A key characteristic to consider when choosing an antibiotic for treatment is its mode of action: bacteriostatic (growth-inhibiting) or bactericidal (mortality-inducing). We present a theoretical model comparing the efficacy of bacteriostatic, bactericidal, and intermediate drugs at preventing the evolutionary rescue of an initially susceptible bacterial population. We find that, all else equal, in resource-abundant environments, bacteriostatic drugs are best, as they constrain cell divisions and thus allow fewer resistance mutations to occur. This contrasts with the prevailing assumption that bactericidal drugs are best as they actively kill cells. When multiple drugs are employed, using one bacteriostatic and one bactericidal drug is usually optimal, because the cell division rate cannot fall below zero, so there are diminishing returns to bacteriostatic activity from two drugs. Severe resource constraints mean that growth rates are already low, and thus there is less benefit to bacteriostatic drugs further limiting growth, so bactericidal drugs are favoured. If these findings are empirically verified in the laboratory and in vivo, they could significantly guide clinical practice.

在设计抗微生物治疗方案时，一个日益重要的目标是在不损害个别患者预后的情况下，尽量减少耐药性演变的可能性。选择用于治疗的抗生素时要考虑的一个关键特征是其作用方式：抑菌（抑制生长）还是杀菌（诱导死亡）。我们提出了一个理论模型，比较抑菌、杀菌和中间药物在防止最初易感细菌种群的进化拯救方面的功效。我们发现，在其他条件相同的情况下，在资源丰富的环境中，抑菌药物是最好的，因为它们限制细胞分裂，从而允许更少的耐药突变发生。这与流行的假设相反，即杀菌药物是最好的，因为它们能主动杀死细胞。当使用多种药物时，使用一种抑菌药和一种杀菌药通常是最佳的，因为细胞分裂率不能低于零，所以两种药物的抑菌活性回报递减。严重的资源限制意味着生长速度已经很低，因此进一步限制生长的抑菌药物的益处较小，因此更倾向于使用杀菌药物。如果这些发现在实验室和体内得到实证验证，将对临床实践具有重要指导意义。

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引用次数: 0