BioCircuits Institute, University of California, San Diego, San Diego, United States.
San Diego Center for Systems Biology, University of California, San Diego, San Diego, United States.
Elife. 2017 Nov 1;6:e25950. doi: 10.7554/eLife.25950.
Horizontal gene transfer (HGT) plays a major role in the spread of antibiotic resistance. Of particular concern are bacteria, which recently emerged as global pathogens, with nosocomial mortality rates reaching 19-54% (Centers for Disease Control and Prevention, 2013; Joly Guillou, 2005; Talbot et al., 2006). gains antibiotic resistance remarkably rapidly (Antunes et al., 2014; Joly Guillou, 2005), with multi drug-resistance (MDR) rates exceeding 60% (Antunes et al., 2014; Centers for Disease Control and Prevention, 2013). Despite growing concern (Centers for Disease Control and Prevention, 2013; Talbot et al., 2006), the mechanisms underlying this extensive HGT remain poorly understood (Adams et al., 2008; Fournier et al., 2006; Imperi et al., 2011; Ramirez et al., 2010; Wilharm et al., 2013). Here, we show bacterial predation by increases cross-species HGT by orders of magnitude, and we observe predator cells functionally acquiring adaptive resistance genes from adjacent prey. We then develop a population-dynamic model quantifying killing and HGT on solid surfaces. We show DNA released via cell lysis is readily available for HGT and may be partially protected from the environment, describe the effects of cell density, and evaluate potential environmental inhibitors. These findings establish a framework for understanding, quantifying, and combating HGT within the microbiome and the emergence of MDR super-bugs.
水平基因转移 (HGT) 在抗生素耐药性的传播中起着重要作用。特别值得关注的是,细菌最近作为全球性病原体出现,医院死亡率达到 19-54%(疾病控制和预防中心,2013 年;Joly Guillou,2005 年;Talbot 等人,2006 年)。能够非常迅速地获得抗生素耐药性(Antunes 等人,2014 年;Joly Guillou,2005 年),多药耐药 (MDR) 率超过 60%(Antunes 等人,2014 年;疾病控制和预防中心,2013 年)。尽管人们越来越关注(疾病控制和预防中心,2013 年;Talbot 等人,2006 年),但这种广泛的 HGT 背后的机制仍知之甚少(Adams 等人,2008 年;Fournier 等人,2006 年;Imperi 等人,2011 年;Ramirez 等人,2010 年;Wilharm 等人,2013 年)。在这里,我们展示了 通过细菌捕食,跨物种 HGT 增加了几个数量级,并且我们观察到捕食细胞从相邻的猎物中获得了适应性的抗性基因。然后,我们开发了一种量化固体表面上杀伤和 HGT 的群体动力学模型。我们表明,通过细胞裂解释放的 DNA 可用于 HGT,并且可能部分受到环境的保护,描述了细胞密度的影响,并评估了潜在的环境抑制剂。这些发现为理解、量化和打击微生物组内的 HGT 以及 MDR 超级细菌的出现奠定了框架。