Insights into the environmental resistance gene pool from the genome sequence of the multidrug-resistant environmental isolate Escherichia coli SMS-3-5

Insights into the environmental resistance gene pool from the genome sequence of the multidrug-resistant environmental isolate Escherichia coli SMS-3-5
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DOI:
10.1128/jb.00661-08
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发表时间:
2008-10-01
影响因子:
3.2
通讯作者:
Stepanauskas, Ramunas
Stepanauskas, Ramunas
中科院分区:
生物学3区
文献类型:
--
作者:
Fricke, W. Florian;Wright, Meredith S.;Stepanauskas, Ramunas

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具有临床和农业重要性的多重耐药病原体越来越多地出现,这是一个全球公共卫生问题。虽然已知在人类和兽医中使用抗菌剂有助于抗菌素耐药性的传播,但微生物群落和来自环境的移动抗药性基因在这一过程中的影响尚不清楚。从工业污染的水环境中分离出来的大肠杆菌SMS-3-5对所有主要类别的抗菌素具有创纪录数量的抗药性,包括两种一线氟喹诺酮类药物(环丙沙星和莫西沙星),在许多情况下达到创纪录的高浓度。为了深入了解环境细菌群体中的抗菌素耐药性,我们对大肠杆菌SMS-3-5的基因组进行了测序,并将其与其他大肠杆菌菌株的基因组序列进行了比较。此外,还对从大肠杆菌SMS-3-5中筛选出的与抗菌素耐药性相关的基因座进行了表型分析。利用鸟枪法测序文库中的重组载体克隆,将对四环素、链霉素和磺胺/甲氧苄啶的抗性归于130kb的单个嵌合区(PSMS35_130)。其余的质粒骨架与禽致病性大肠杆菌(APEC)菌株的毒力质粒有相似性。PSMS35_130的个体耐药基因盒在来自多个系统发育和地理来源的耐药菌株中保守。对喹诺酮类药物的耐药性被分配到几个染色体位点,主要编码运输系统,这些系统也存在于敏感的大肠杆菌分离株中。因此,大肠杆菌SMS-3-5的耐药性既取决于从临床和农业病原体可能获得的移动基因库获得的决定因素,也取决于特定适应的多药外排系统。PSMS35_130上的抗菌素耐药性与APEC毒力基因的关联突出了通过广泛使用抗生素促进毒力传播的风险。
The increasing occurrence of multidrug-resistant pathogens of clinical and agricultural importance is a global public health concern. While antimicrobial use in human and veterinary medicine is known to contribute to the dissemination of antimicrobial resistance, the impact of microbial communities and mobile resistance genes from the environment in this process is not well understood. Isolated from an industrially polluted aquatic environment, Escherichia coli SMS-3-5 is resistant to a record number of antimicrobial compounds from all major classes, including two front-line fluoroquinolones (ciprofloxacin and moxifloxacin), and in many cases at record-high concentrations. To gain insights into antimicrobial resistance in environmental bacterial populations, the genome of E. coli SMS-3-5 was sequenced and compared to the genome sequences of other E. coli strains. In addition, selected genetic loci from E. coli SMS-3-5 predicted to be involved in antimicrobial resistance were phenotypically characterized. Using recombinant vector clones from shotgun sequencing libraries, resistance to tetracycline, streptomycin, and sulfonamide/ trimethoprim was assigned to a single mosaic region on a 130-kb plasmid (pSMS35_130). The remaining plasmid backbone showed similarity to virulence plasmids from avian-pathogenic E. coli (APEC) strains. Individual resistance gene cassettes from pSMS35_130 are conserved among resistant bacterial isolates from multiple phylogenetic and geographic sources. Resistance to quinolones was assigned to several chromosomal loci, mostly encoding transport systems that are also present in susceptible E. coli isolates. Antimicrobial resistance in E. coli SMS-3-5 is therefore dependent both on determinants acquired from a mobile gene pool that is likely available to clinical and agricultural pathogens, as well, and on specifically adapted multidrug efflux systems. The association of antimicrobial resistance with APEC virulence genes on pSMS35_130 highlights the risk of promoting the spread of virulence through the extensive use of antibiotics.