Gianvecchio Crystal, Lozano Natalie Ann, Henderson Claire, Kalhori Pooneh, Bullivant Austin, Valencia Alondra, Su Lauren, Bello Gladys, Wong Michele, Cook Emoni, Fuller Lakhia, Neal Jerome B, Yeh Pamela J
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA, United States.
Santa Fe Institute, Santa Fe, NM, United States.
Front Microbiol. 2019 Jan 31;10:42. doi: 10.3389/fmicb.2019.00042. eCollection 2019.
Understanding how phenotypic traits vary has been a longstanding goal of evolutionary biologists. When examining antibiotic-resistance in bacteria, it is generally understood that the minimum inhibitory concentration (MIC) has minimal variation specific to each bacterial strain-antibiotic combination. However, there is a less studied resistance trait, the mutant prevention concentration (MPC), which measures the MIC of the most resistant sub-population. Whether and how MPC varies has been poorly understood. Here, we ask a simple, yet important question: How much does the MPC vary, within a single strain-antibiotic association? Using a species and five antibiotics from five different antibiotic classes-ciprofloxacin, doxycycline, gentamicin, nitrofurantoin, and oxacillin-we examined the frequency of resistance for a wide range of concentrations per antibiotic, and measured the repeatability of the MPC, the lowest amount of antibiotic that would ensure no surviving cells in a 10 population of bacteria. We found a wide variation within the MPC and distributions that were rarely normal. When antibiotic resistance evolved, the distribution of the MPC changed, with all distributions becoming wider and some multi-modal. Unlike the MIC, there is high variability in the MPC for a given bacterial strain-antibiotic combination.
理解表型性状如何变化一直是进化生物学家长期以来的目标。在研究细菌的抗生素耐药性时，通常认为最低抑菌浓度（MIC）对于每种细菌菌株 - 抗生素组合具有最小的变异性。然而，有一种研究较少的耐药性状，即突变预防浓度（MPC），它衡量的是最耐药亚群的MIC。MPC是否以及如何变化一直鲜为人知。在这里，我们提出一个简单却重要的问题：在单一菌株 - 抗生素组合中，MPC的变化有多大？我们使用一种细菌物种以及来自五种不同抗生素类别的五种抗生素——环丙沙星、强力霉素、庆大霉素、呋喃妥因和苯唑西林——检测了每种抗生素在广泛浓度范围内的耐药频率，并测量了MPC的重复性，MPC是能确保在10个细菌群体中无存活细胞所需的最低抗生素量。我们发现MPC存在广泛的变异性，且分布很少呈正态分布。当抗生素耐药性进化时，MPC的分布发生了变化，所有分布都变宽了，有些还呈现多峰分布。与MIC不同，对于给定的细菌菌株 - 抗生素组合，MPC具有很高的变异性。
