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广泛的查揭示了人类病原体中以前未被发现的氨基糖化物耐药基因

David Lund^1,2, Roelof Dirk Coertze^2,3, Marcos Parras-Moltó^1,2

¹Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden.

Communications biology

|August 3, 2023

概括

细菌基因组的计算查发现了新的抗生素耐药性基因 (ARG). 在病原体中发现新的氨基糖化物修饰酶 (AMEs) 的这一发现有助于早期检测和打击抗菌素耐药性的传播.

科学领域:

基因组学就是基因组学.
微生物学微生物学
计算生物学计算生物学
抗微生物耐药性抗微生物耐药性

背景情况:

抗生素耐药性是一个重大的全球健康威胁,由于抗生素耐药性基因 (ARG) 通过水平基因转移的传播而加剧.
新兴的ARG通常在广泛传播之前不会被发现,从而阻碍了有效的控制策略.
氨基糖化物修饰酶 (AME) 是一种关键的耐药性决定因子.

研究的目的:

通过计算选大量细菌基因组数据集,以发现以前未知的移动抗生素耐药性基因 (ARG).
识别具有潜在临床意义的新型氨基糖化物修饰酶 (AME).
展示计算方法对新出现的ARG的早期检测的实用性.

主要方法:

大规模对大约100万个细菌基因组进行计算选.
预测和聚类的氨基糖酶修饰酶 (AME) 基因.
生物信息分析以确定与移动遗传元素和致病宿主相关的新型AME家族.
预测EME对大肠杆菌中氨基糖化物耐药性的实验验证.

主要成果:

鉴定了1,071,815个预测基因,它们编码了34,053个独特的氨基糖化物修饰酶 (AME),分为7,612个家族.
发现了50个与移动遗传元素和致病细菌相关的新型AMEE家族,只有88个以前描述的家族被发现.
实验测试证实,28种新型AME中24种在大肠杆菌中赋予了氨基糖化物耐药性,其中17种表现出超过临床断点的耐药性.

结论:

这项研究显著扩大了已知的临床相关的氨基糖化物耐药性决定因素的范围.
计算查是一种有效的方法,用于早期发现可能出现的抗生素耐药性基因.
鉴定到的新型外来 AME 是未来监测和治疗抗抗菌素耐药性战略的潜在目标.

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