The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains of Escherichia coli
The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains of Escherichia coli
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DOI：
10.1128/aac.00635-19
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发表时间：
2019-08-01
影响因子：
4.9
通讯作者：
Branger, Catherine
中科院分区：
文献类型：
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作者：
Billard-Pomares, Typhaine;Clermont, Olivier;Branger, Catherine
我们之前在大肠杆菌 0102-ST405 菌株的 CTX-M 生产质粒上鉴定了一个参与精氨酸脱亚胺酶 (ADI) 途径的操纵子（弧操纵子）。由于 ADI 途径被证明与各种革兰氏阳性细菌的毒力有关，因此我们测试了 ADI 途径是否可能与产生超广谱 β-内酰胺酶 (ESBL) 的大肠杆菌菌株的流行病学成功有关。我们研究了在法国 (n = 493) 和英国 (n = 1,509) 分离的两个人类大肠杆菌样本，结果表明，弧操纵子的流行率 (i) 产 ESBL 菌株 (12.1%) 高于非产 ESBL 菌株 (2.5%)，(ii) 产 CTX-M 菌株 (16%) 高于其他产 ESBL 菌株 (3.5%)，(iii) 随着时间的推移，弧操纵子的患病率增加产 ESBL 菌株从 2000 年之前的 0% 增加到 2011 年至 2012 年的 43.3%。在来自不同系统发育背景的菌株中发现的弧操纵子由 IncE 质粒 (85%) 或染色体 (15%) 携带，位于由大量插入序列构成的区域，表明多次到达。竞争实验表明，弧操纵子增强了菌株在含有精氨酸的溶源肉汤中的体外适应性。体内竞争实验表明，弧操纵子对于尿路感染（UTI）小鼠模型中的菌株是有利的，而对于肠道定植小鼠模型中则是负担。总之，我们已经确定了与产生 CTX-M 的菌株相关的一个性状，该性状负责两种主要大肠杆菌生活方式（尿路感染和肠道共生）之间的权衡。仅这一特征无法解释 ESBL 在大肠杆菌中的广泛传播，但值得流行病学监测。
We previously identified an operon involved in an arginine deiminase (ADI) pathway (arc operon) on a CTX-M-producing plasmid from an 0102-ST405 strain of Escherichia coll. As the ADI pathway was shown to be involved in the virulence of various Gram-positive bacteria, we tested whether the ADI pathway could be involved in the epidemiological success of extended-spectrum-beta-lactamase (ESBL)-producing E. coli strains. We studied two collections of human E. coli isolated in France (n = 493) and England (n = 1,509) and show that the prevalence of the arc operon (i) is higher in ESBL-producing strains (12.1%) than in nonproducers (2.5%), (ii) is higher in CTX-M-producing strains (16%) than in other ESBL producers (3.5%), and (iii) increased over time in ESBL-producing strains from 0% before 2000 to 43.3% in 2011 to 2012. The arc operon, found in strains from various phylogenetic backgrounds, is carried by IncE plasmids (85%) or chromosomes (15%) in regions framed by numerous insertion sequences, indicating multiple arrivals. Competition experiments showed that the arc operon enhances fitness of the strain in vitro in lysogeny broth with arginine. In vivo competition experiments showed that the arc operon is advantageous for the strain in a mouse model of urinary tract infection (UTI), whereas it is a burden in a mouse model of intestinal colonization. In summary, we have identified a trait linked to CTX-M-producing strains that is responsible for a trade-off between two main E. coil lifestyles, UTI and gut commensalism. This trait alone cannot explain the wide spread of ESBLs in E. coli but merits epidemiological surveillance.