Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli
Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli
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DOI：
10.1038/s41522-019-0109-2
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发表时间：
2019-11-29
影响因子：
9.2
通讯作者：
Raymond, Ben
中科院分区：
文献类型：
--
作者：
Amanatidou, Elli;Matthews, Andrew C.;Raymond, Ben
革兰氏阴性菌，如大肠埃希氏菌，通常使用质粒编码的β-内酰胺酶耐药。已经发现，表达β-内酰胺酶的细菌菌株可以使液体培养物解毒，从而保护遗传敏感的菌株，这构成了社会保护的一个明显的实验室例子。这些结果不一定是普遍的；例如，在固体媒体上，β-内酰胺类药物的快速杀菌作用在很大程度上阻碍了社会保护。在这里，我们测试了这样一个假设，即生物被膜细菌对β-内酰胺类药物的更大耐受性将促进社会互动。我们使用了一株最近分离的能够形成强大生物膜的大肠杆菌菌株，来比较在菌落生物膜和肉汤培养中的合作和开发如何驱动编码临床上重要的β-内酰胺酶的非结合质粒的动态。生物膜中的敏感细胞对高剂量的氨苄西林耐受，需要几天的暴露才能杀死它们。为了支持我们的假设，我们在生物膜中发现了对敏感大肠杆菌的强大社会保护，尽管耐药和敏感细胞的精细物理分离和较低的胞外β-内酰胺酶产生率。相比之下，肉汤中的社会互动被限制在相对较小的氨苄西林剂量范围内。我们的结果表明，革兰氏阴性生物膜上的β-内酰胺类选择压力导致了协同耐药，其特征是耐药质粒的平衡频率较低，足以保护所有细胞。
Gram-negative bacteria such as Escherichia coli commonly resist beta-lactam antibiotics using plasmid-encoded beta-lactamase enzymes. Bacterial strains that express beta-lactamases have been found to detoxify liquid cultures and thus to protect genetically susceptible strains, constituting a clear laboratory example of social protection. These results are not necessarily general; on solid media, for instance, the rapid bactericidal action of beta-lactams largely prevents social protection. Here, we tested the hypothesis that the greater tolerance of biofilm bacteria for beta-lactams would facilitate social interactions. We used a recently isolated E. coli strain, capable of strong biofilm formation, to compare how cooperation and exploitation in colony biofilms and broth culture drives the dynamics of a non-conjugative plasmid encoding a clinically important beta-lactamase. Susceptible cells in biofilms were tolerant of ampicillin-high doses and several days of exposure were required to kill them. In support of our hypothesis, we found robust social protection of susceptible E. coli in biofilms, despite fine-scale physical separation of resistant and susceptible cells and lower rates of production of extracellular beta-lactamase. In contrast, social interactions in broth were restricted to a relatively narrow range of ampicillin doses. Our results show that beta-lactam selection pressure on Gram-negative biofilms leads to cooperative resistance characterized by a low equilibrium frequency of resistance plasmids, sufficient to protect all cells.