Growth rate assays reveal fitness consequences of β-lactamases

Clinical resistance determination is critical for monitoring the spread of antibiotic resistance. However, clinical methods of detecting resistance lack the sensitivity necessary to make strong conclusions about fitness. Growth rates are a far more sensitive method of measuring resistance, but they differ from clinical methods in that a single concentration of antibiotic is used for the assay. Here we show that in spite of this key difference, the results of growth rates correlate well with clinical determination of resistance by MIC, while providing the sensitivity required for direct input as fitness values into mathematical models. By measuring the growth rates of sequenced clinical isolates obtained from Dignity Health Mercy Medical Center, we additionally detected the fitness effects of individual resistance genes on bacteria as they are exposed to different antibiotics. In our study, the CTX-M-15 gene conferred the highest fitness; the TEM-1 gene decreased fitness and the OXA-1 ge...临床耐药性检测对于监测抗生素耐药性的传播至关重要。然而，现有临床耐药检测方法缺乏足够的灵敏度，无法针对细菌适合度得出严谨结论。生长速率测定法对耐药性的检测灵敏度远高于临床方法，但该方法与临床检测的差异在于，其实验仅使用单一浓度的抗生素开展测定。本研究表明，尽管存在这一关键差异，生长速率测定结果与通过最低抑菌浓度（Minimum Inhibitory Concentration, MIC）进行的临床耐药性检测结果具有良好的相关性，同时其灵敏度足以直接将适合度数值输入数学模型。本研究通过对取自尊严健康慈悲医疗中心（Dignity Health Mercy Medical Center）的已测序临床分离株进行生长速率测定，额外分析了单一耐药基因在细菌暴露于不同抗生素时对细菌适合度的影响。本研究中，CTX-M-15基因可赋予细菌最高的适合度；TEM-1基因会降低细菌适合度，而OXA-1基因……