Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mol Syst Biol. 2013 Aug 6;9:683. doi: 10.1038/msb.2013.39.
Inactivation of β-lactam antibiotics by resistant bacteria is a 'cooperative' behavior that may allow sensitive bacteria to survive antibiotic treatment. However, the factors that determine the fraction of resistant cells in the bacterial population remain unclear, indicating a fundamental gap in our understanding of how antibiotic resistance evolves. Here, we experimentally track the spread of a plasmid that encodes a β-lactamase enzyme through the bacterial population. We find that independent of the initial fraction of resistant cells, the population settles to an equilibrium fraction proportional to the antibiotic concentration divided by the cell density. A simple model explains this behavior, successfully predicting a data collapse over two orders of magnitude in antibiotic concentration. This model also successfully predicts that adding a commonly used β-lactamase inhibitor will lead to the spread of resistance, highlighting the need to incorporate social dynamics into the study of antibiotic resistance.
耐药细菌对β-内酰胺类抗生素的失活是一种“合作”行为，可能使敏感细菌在抗生素治疗中存活下来。然而，决定细菌种群中耐药细胞比例的因素尚不清楚，这表明我们对抗生素耐药性如何演变的理解存在根本差距。在这里，我们通过实验跟踪了编码β-内酰胺酶的质粒在细菌种群中的传播。我们发现，与初始耐药细胞的比例无关，种群会稳定到一个与抗生素浓度除以细胞密度成正比的平衡比例。一个简单的模型解释了这种行为，成功地预测了抗生素浓度两个数量级的数据崩溃。该模型还成功地预测了添加常用的β-内酰胺酶抑制剂将导致耐药性的传播，这突出表明需要将社会动态纳入抗生素耐药性的研究中。
