Myhrvold Cameron, Kotula Jonathan W, Hicks Wade M, Conway Nicholas J, Silver Pamela A
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.
Nat Commun. 2015 Nov 30;6:10039. doi: 10.1038/ncomms10039.
Microbial population growth is typically measured when cells can be directly observed, or when death is rare. However, neither of these conditions hold for the mammalian gut microbiota, and, therefore, standard approaches cannot accurately measure the growth dynamics of this community. Here we introduce a new method (distributed cell division counting, DCDC) that uses the accurate segregation at cell division of genetically encoded fluorescent particles to measure microbial growth rates. Using DCDC, we can measure the growth rate of Escherichia coli for >10 consecutive generations. We demonstrate experimentally and theoretically that DCDC is robust to error across a wide range of temperatures and conditions, including in the mammalian gut. Furthermore, our experimental observations inform a mathematical model of the population dynamics of the gut microbiota. DCDC can enable the study of microbial growth during infection, gut dysbiosis, antibiotic therapy or other situations relevant to human health.
微生物种群增长通常在能够直接观察细胞或死亡情况罕见时进行测量。然而，这两种情况在哺乳动物肠道微生物群中都不成立，因此，标准方法无法准确测量该群落的生长动态。在此，我们引入一种新方法（分布式细胞分裂计数法，DCDC），该方法利用基因编码荧光颗粒在细胞分裂时的精确分离来测量微生物生长速率。使用DCDC，我们能够连续超过10代测量大肠杆菌的生长速率。我们通过实验和理论证明，DCDC在广泛的温度和条件范围内，包括在哺乳动物肠道中，对误差具有鲁棒性。此外，我们的实验观察为肠道微生物群种群动态的数学模型提供了依据。DCDC能够用于研究感染、肠道生态失调、抗生素治疗或其他与人类健康相关情况下的微生物生长。
