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...