最新研究显示,引起肺炎和脑膜炎的细菌会非常快速地改头换面,灵敏地产生对抗菌素和疫苗的抵抗力。
古往今来,肺炎链球菌一直是造成人类死亡的一个主要原因。出现在全世界的肺炎链球菌西班牙23F菌株是一个对多种抗菌素有抵抗力的特别棘手的菌株。幸运地是,这一世系的菌株分离物自1984年以来已经在全世界多个地点被收集起来,Nicholas Croucher及其同事利用这些收集的菌株来仔细地剖析其演变过程。该国际性研究团队用高通量测序技术对200多个分离株的基因组进行了测序和比较。
结果显示,自1984年以来,该细菌已经用重组(即在细胞分裂时将基因组做混合改组)和碱基置换(这是将个体DNA“字母”进行调换的突变)这两种方法已经翻转了其约四分之三的基因组。这一敏捷的基因变化使得该病原体能够躲避诸如疫苗和抗菌素等公共健康措施的影响。在一则相关的观点栏目中,Mark C. Enright 与Brian G. Spratt将这一研究方法的功效与先前研究的功效进行了对比。
先前的研究所分析的只是每个分离物中的少许基因。而最近的这一研究显示了细菌在非常短的时期中是如何变化的,这对人们理解和预测病原体对新的抗菌素和疫苗的反应是重要的。(生物谷Bioon.com)
原文出处:
Science Vol. 331 no. 6016 pp. 430-434 DOI: 10.1126/science.1198545
Rapid Pneumococcal Evolution in Response to Clinical Interventions
Nicholas J. Croucher1, Simon R. Harris1, Christophe Fraser2, Michael A. Quail1, John Burton1, Mark van der Linden3, Lesley McGee4, Anne von Gottberg5, Jae Hoon Song6, Kwan Soo Ko7, Bruno Pichon8, Stephen Baker9, Christopher M. Parry9, Lotte M. Lambertsen10, Dea Shahinas11, Dylan R. Pillai11, Timothy J. Mitchell12, Gordon Dougan1, Alexander Tomasz13, Keith P. Klugman4,5,14, Julian Parkhill1, William P. Hanage2,15, and Stephen D. Bentley1,*
Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain23F-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. More than 700 recombinations were detected, with genes encoding major antigens frequently affected. Among these were 10 capsule-switching events, one of which accompanied a population shift as vaccine-escape serotype 19A isolates emerged in the USA after the introduction of the conjugate polysaccharide vaccine. The evolution of resistance to fluoroquinolones, rifampicin, and macrolides was observed to occur on multiple occasions. This study details how genomic plasticity within lineages of recombinogenic bacteria can permit adaptation to clinical interventions over remarkably short time scales.