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With increasing resolution of microbial diversity at the genomic level, experimental and modeling frameworks that translate such diversity into phenotypes are highly needed. This is particularly important when comparing drug-resistant with drug-sensitive pathogen strains, when anticipating epidemiological implications of microbial diversity, and when designing control measures. Classical approaches quantify differences between microbial strains using the exponential growth model, and typically report a selection coefficient for the relative fitness differential between two strains. The apparent simplicity of such approaches comes with the costs of limiting the range of biological scenarios that can be captured, and biases strain fitness estimates to polarized extremes of competitive exclusion. Here, we propose a mathematical and statistical framework based on the Lotka-Volterra model, that can capture frequency-dependent competition between microbial strains within-host and upon transmission. As a  proof-of-concept , the model is applied to a previously-published dataset from  in-vivo  competitive mixture experiments with influenza strains in ferrets (McCaw et al.,  2011 ). We show that for the same data, our model predicts a scenario of coexistence between strains, and supports a higher bottleneck size in the range of 35–145 virions transmitted from donor to recipient host. Thanks to its simplicity and generality, such framework could be applied to other ecological scenarios of microbial competition, enabling a more complex and nuanced view of possible outcomes between two strains, beyond competitive exclusion.

Modeling Competitive Mixtures With the Lotka-Volterra Framework for More Complex Fitness Assessment Between Strains