Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, Instituto Universitario de Investigación en Ciencias de la Salud, Palma de Mallorca, Spain.
Clin Microbiol Infect. 2010 Jul;16(7):798-808. doi: 10.1111/j.1469-0691.2010.03250.x.
Hypermutable or mutator microorganisms are those that have an increased spontaneous mutation rate as a result of defects in DNA repair or error avoidance systems. Over the last two decades, several studies have provided strong evidence for a relevant role of mutators in the evolution of natural bacterial populations, particularly in the field of infectious diseases. Among them, chronic respiratory infection with Pseudomonas aeruginosa in cystic fibrosis (CF) patients was the first natural environment to reveal the high prevalence and important role of mutators. A remarkable positive selection of mutators during the course of the chronic infection has been reported, mainly as a result of the emergence of DNA mismatch repair system (mutS, mutL or mutU)-deficient mutants, although strains defective in the GO system (mutM, mutY and mutT) have also been observed. High frequencies of mutators have also been noted among other pathogens in the CF setting, particularly Staphylococcus aureus and Haemophilus influenzae. Enhanced antimicrobial resistance development is the most thoroughly studied consequence of mutators in CF and other chronic infections, although recent studies show that mutators may additionally have important effects on the evolution of virulence, genetic adaptation to the airways of CF patients, persistence of colonization, transmissibility, and perhaps lung function decline. Further prospective clinical studies are nevertheless still needed for an in-depth evaluation of the impact of mutators on disease progression and outcome.
高突变或突变体微生物是指由于 DNA 修复或错误避免系统的缺陷而导致自发突变率增加的微生物。在过去的二十年中，有几项研究为突变体在自然细菌种群的进化中特别是在传染病领域中的相关作用提供了强有力的证据。其中，囊性纤维化 (CF) 患者肺部的铜绿假单胞菌慢性呼吸道感染是第一个揭示突变体高流行率和重要作用的自然环境。据报道，在慢性感染过程中突变体经历了显著的正选择，主要是由于 DNA 错配修复系统 (mutS、mutL 或 mutU) 缺陷突变体的出现，尽管 GO 系统缺陷菌株 (mutM、mutY 和 mutT) 也被观察到。在 CF 环境中，其他病原体如金黄色葡萄球菌和流感嗜血杆菌中也观察到了高突变体频率。增强的抗菌药物耐药性发展是 CF 和其他慢性感染中突变体最彻底的研究后果，尽管最近的研究表明，突变体可能对毒力的进化、对 CF 患者气道的遗传适应、定植的持久性、传染性以及肺功能下降具有重要影响。然而，为了深入评估突变体对疾病进展和结局的影响，仍需要进一步的前瞻性临床研究。
