Viberg Linda T, Sarovich Derek S, Kidd Timothy J, Geake James B, Bell Scott C, Currie Bart J, Price Erin P
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.
mBio. 2017 Apr 11;8(2):e00356-17. doi: 10.1128/mBio.00356-17.
Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium , the causative agent of melioidosis. Here, we compared the genomes of isolates collected between ~4 and 55 months apart from seven chronically infected CF patients. Overall, the strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our report highlights the exquisite adaptability of microorganisms to long-term persistence in their environment and the ongoing challenges of antibiotic treatment in eradicating pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a degree of predictability in bacterial evolution in the CF lung and potential targeted eradication of chronic CF infections in the future., the causative agent of melioidosis, is an environmental opportunistic bacterium that typically infects immunocompromised people and those with certain risk factors such as cystic fibrosis (CF). Patients with CF tend to develop chronic melioidosis infections, for reasons that are not well understood. This report is the first to describe evolution within the CF lung during chronic infection. We show that the pathways by which adapts to the CF lung are similar to those seen in better-studied CF pathogens such as , , and complex species. Adaptations include the accumulation of antibiotic resistance, loss of nonessential genes, metabolic alterations, and virulence factor attenuation. Known and novel mechanisms of resistance to three of the five antibiotics used in melioidosis treatment were identified. Similar pathways of evolution in CF pathogens, including , provide exciting avenues for more-targeted treatment of chronic, recalcitrant infections.
囊性纤维化（CF）是一种以肺功能进行性下降为特征的遗传性疾病。CF患者发生呼吸道感染的风险增加，包括由环境细菌（类鼻疽病的病原体）引起的感染。在此，我们比较了从7例慢性感染CF患者中在约4至55个月期间采集的 分离株的基因组。总体而言， 菌株显示出与其他慢性感染相似的进化模式，包括抗生素耐药性的出现、基因组缩减以及参与毒力、代谢、环境生存和细胞壁成分的基因中的有害突变。我们记录了首次报道的 高突变体，这可能是由有缺陷的MutS引起的。此外，我们的研究确定了对类鼻疽病治疗中五种临床重要抗生素中的三种产生耐药性的已知和新的分子机制。我们的报告强调了微生物对其环境中长期生存的卓越适应性以及在根除CF肺部病原体方面抗生素治疗面临的持续挑战。与其他CF病原体的趋同进化暗示了CF肺部细菌进化的一定程度的可预测性以及未来潜在的针对性根除慢性CF感染的可能性。，类鼻疽病的病原体，是一种环境机会性细菌，通常感染免疫功能低下的人和有某些风险因素的人，如囊性纤维化（CF）患者。CF患者往往会发生慢性类鼻疽病感染，原因尚不清楚。本报告首次描述了慢性感染期间CF肺部内 的进化。我们表明， 适应CF肺部的途径与在研究得更深入的CF病原体如 、 和 复合物种中看到的途径相似。适应包括抗生素耐药性的积累、非必需基因的丢失、代谢改变和毒力因子减弱。确定了对类鼻疽病治疗中使用的五种抗生素中的三种产生耐药性的已知和新机制。CF病原体（包括 ）中相似的进化途径为更有针对性地治疗慢性顽固性感染提供了令人兴奋的途径。
