Multifactorial Competition and Resistance in a Two-Species Bacterial System.
Multifactorial Competition and Resistance in a Two-Species Bacterial System.
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DOI：
10.1371/journal.pgen.1005715
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发表时间：
2015-12
期刊：
影响因子：
4.5
通讯作者：
Tavazoie S
中科院分区：
文献类型：
--
作者：
Khare A;Tavazoie S
微生物几乎完全存在于相互作用的多物种群落中，但相互作用的细菌的适合性和可获得的适应途径的遗传决定因素仍未确定。本文采用二种群系统，研究了铜绿假单胞菌对大肠杆菌的拮抗作用。我们不偏不倚的基因组规模方法使我们能够确定解释所观察到的整个对抗的多种因素。我们发现了这两种形式的生态竞争--铁的封存导致剥削性竞争，而奋乃静暴露则产生干扰竞争。我们使用实验室进化来发现我们系统中的适应性进化轨迹。在铜绿假单胞菌毒素存在的情况下，大肠杆菌种群在基因水平上表现出平行的分子进化和适应性收敛。已发现的多种抗性途径为了解毒素进入和活性的机制提供了新的见解。我们的研究揭示了简单的两个物种相互作用的分子复杂性，这是应用系统生物学详细分子解剖本地微生物群内相互作用的重要第一步。细菌通常作为大型多物种群落的一部分存在于自然界中，它们的行为通过分泌分子或身体接触受到周围物种的影响。人们对这种相互作用知之甚少，而且很少有人研究在任何多物种系统中实际影响细菌生长和行为的途径。在这项研究中，我们证明了条件致病菌铜绿假单胞菌抑制了共生大肠杆菌的生长，并使用无偏见的基因组规模的方法来鉴定介体。我们发现铜绿假单胞菌的铁螯合分子和氧化还原活性吩嗪解释了我们系统中看到的所有大肠杆菌生长抑制。我们还在铜绿假单胞菌抗菌素存在的情况下进化了大肠杆菌，并确定了导致耐药性的多条途径，从而对这些抗菌分子的作用机制有了新的见解。因此，我们的研究展示了即使是简单的两种细菌系统的复杂性，并为在分子水平上研究这种相互作用奠定了框架。
Microorganisms exist almost exclusively in interactive multispecies communities, but genetic determinants of the fitness of interacting bacteria, and accessible adaptive pathways, remain uncharacterized. Here, using a two-species system, we studied the antagonism of Pseudomonas aeruginosa against Escherichia coli. Our unbiased genome-scale approach enabled us to identify multiple factors that explained the entire antagonism observed. We discovered both forms of ecological competition–sequestration of iron led to exploitative competition, while phenazine exposure engendered interference competition. We used laboratory evolution to discover adaptive evolutionary trajectories in our system. In the presence of P. aeruginosa toxins, E. coli populations showed parallel molecular evolution and adaptive convergence at the gene-level. The multiple resistance pathways discovered provide novel insights into mechanisms of toxin entry and activity. Our study reveals the molecular complexity of a simple two-species interaction, an important first-step in the application of systems biology to detailed molecular dissection of interactions within native microbiomes. Bacteria commonly exist in nature as part of large multispecies communities, and their behavior is affected by the surrounding species via secreted molecules or physical contact. Such interactions are poorly understood, and the pathways that actually affect bacterial growth and behavior in any multispecies system have rarely been studied. In this study, we show that the opportunistic pathogen Pseudomonas aeruginosa inhibits the growth of the commensal Escherichia coli, and we use unbiased genome-scale methods to identify the mediators. We find that P. aeruginosa iron-chelating molecules and redox-active phenazines account for all of the E. coli growth inhibition seen in our system. We also evolve E. coli in the presence of the P. aeruginosa antimicrobials and identify multiple pathways that lead to resistance, gaining novel insights into the mechanism of action of these antimicrobial molecules. Thus, our study demonstrates the complexity of even simple two-species bacterial systems and lays down a framework for studying such interactions at the molecular level.