On the meaning and estimation of plasmid transfer rates for surface-associated and well-mixed bacterial populations.

On the meaning and estimation of plasmid transfer rates for surface-associated and well-mixed bacterial populations.
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DOI:
10.1016/j.jtbi.2011.10.034
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发表时间:
2012-02-07
影响因子:
2
通讯作者:
Krone, Stephen M.
Krone, Stephen M.
中科院分区:
生物学4区
文献类型:
--
作者:
Zhong, Xue;Droesch, Jason;Fox, Randal;Top, Eva M.;Krone, Stephen M.

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接合性质粒转移是细菌快速适应新环境的关键,但对质粒转移速率的单一定量测量没有一致意见。一些研究从质粒群体生物学的质量作用微分方程模型中获得转移速率的估计。经常使用的“端点方法”就是这样一个例子。其他报告的质粒转移效率的措施,简单地代表质粒轴承和无质粒的细胞密度的比率,并不对应于任何数学模型中的参数。不幸的是,这些量并不能衡量同一件事--有时在数量级上有所不同--而且它们的使用往往因缺乏特异性而蒙上阴影。此外,它们没有区分仅在充分混合的群体中相关的整体转移速率和单个细胞之间的“内在”速率。这导致了表面相关人口的问题,这不是很好地混合,但空间结构。我们使用了一个空间显式的数学模型来评估这些不同的质粒转移效率的措施,当它们被应用到表面相关的人口的有效性模拟。一些实验结果支持的模拟结果表明,这些措施可以通过初始细胞密度,供体与受体的比例和初始细胞簇大小的影响,因此作为质粒转移效率的通用措施是有缺陷的。模拟还使我们能够制定一些指导原则,这些估计何时适用于空间结构人口以及如何解释结果。虽然我们专注于质粒转移,但这项研究的一般教训应适用于任何水平扩散的测量(例如,流行病学中的感染率)基于简单的群体作用模型(例如,流行病学中的SIR模型),但适用于空间设置。
Conjugative plasmid transfer is key to the ability of bacteria to rapidly adapt to new environments, but there is no agreement on a single quantitative measure of the rate of plasmid transfer. Some studies derive estimates of transfer rates from mass-action differential equation models of plasmid population biology. The often-used ‘endpoint method’ is such an example. Others report measures of plasmid transfer efficiency that simply represent ratios of plasmid-bearing and plasmid-free cell densities and do not correspond to parameters in any mathematical model. Unfortunately, these quantities do not measure the same thing – sometimes differing by orders of magnitude – and their use is often clouded by a lack of specificity. Moreover, they do not distinguish between bulk transfer rates that are only relevant in well-mixed populations and the ‘intrinsic’ rates between individual cells. This leads to problems for surface-associated populations, which are not well-mixed but spatially structured. We used simulations of a spatially explicit mathematical model to evaluate the effectiveness of these various plasmid transfer efficiency measures when they are applied to surface-associated populations. The simulation results, supported by some experimental findings, showed that these measures can be affected by initial cell densities, donor-to-recipient ratios and initial cell cluster size, and are therefore flawed as universal measures of plasmid transfer efficiency. The simulations also allowed us to formulate some guiding principles on when these estimates are appropriate for spatially structured populations and how to interpret the results. While we focus on plasmid transfer, the general lessons of this study should apply to any measures of horizontal spread (e.g., infection rates in epidemiology) that are based on simple mass-action models (e.g., SIR models in epidemiology) but applied to spatial settings.
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