Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data.
Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data.
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DOI：
10.1098/rsif.2023.0074
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发表时间：
2023-06
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--
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许多细菌病原体群体中抗生素耐药性水平的增加是对公共卫生的主要威胁。当细菌暴露于这种抗生素时，对抗生素的抗性提供了适应性益处，但相对于敏感的对应物，抗性也往往以抗性病原体为代价。我们对许多细菌病原体和抗生素的耐药性的好处和成本缺乏很好的了解，但估计它们可能会导致更好地使用抗生素，以减少或防止耐药性的传播。在这里，我们提出了一个新的模型的联合流行病学的敏感和耐药的变种，其中包括明确的参数的成本和收益的阻力。我们展示了如何贝叶斯推断可以在此模型下使用易感和耐药谱系的系统发育数据进行，并通过结合两者的数据，我们能够解开和估计的阻力成本和效益参数分别。我们将我们的推理方法应用于几个模拟数据集，以证明良好的可扩展性和准确性。我们分析了2000年至2013年在美国收集的淋病奈瑟菌基因组数据集。我们发现，两个不相关的谱系耐氟喹诺酮类药物共享相似的流行动力学和耐药参数。由于耐药性水平的增加，氟喹诺酮类药物被放弃用于治疗淋病，但我们的研究结果表明，它们可以用于治疗约10%的少数病例，而不会导致耐药性再次增长。
Increasing levels of antibiotic resistance in many bacterial pathogen populations are a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria are exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative to susceptible counterparts. We lack a good understanding of these benefits and costs of resistance for many bacterial pathogens and antibiotics, but estimating them could lead to better use of antibiotics in a way that reduces or prevents the spread of resistance. Here, we propose a new model for the joint epidemiology of susceptible and resistant variants, which includes explicit parameters for the cost and benefit of resistance. We show how Bayesian inference can be performed under this model using phylogenetic data from susceptible and resistant lineages and that by combining data from both we are able to disentangle and estimate the resistance cost and benefit parameters separately. We applied our inferential methodology to several simulated datasets to demonstrate good scalability and accuracy. We analysed a dataset of Neisseria gonorrhoeae genomes collected between 2000 and 2013 in the USA. We found that two unrelated lineages resistant to fluoroquinolones shared similar epidemic dynamics and resistance parameters. Fluoroquinolones were abandoned for the treatment of gonorrhoea due to increasing levels of resistance, but our results suggest that they could be used to treat a minority of around 10% of cases without causing resistance to grow again.
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