Transcriptional response of mucoid Pseudomonas aeruginosa to human respiratory mucus.
Transcriptional response of mucoid Pseudomonas aeruginosa to human respiratory mucus.
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DOI：
10.1128/mbio.00410-12
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发表时间：
2013-01-02
期刊：
影响因子：
6.4
通讯作者：
Lory S
中科院分区：
文献类型：
--
作者：
Cattoir V;Narasimhan G;Skurnik D;Aschard H;Roux D;Ramphal R;Jyot J;Lory S
细菌病原体对宿主的适应可以导致其基因组中特定突变的选择和积累，对生物体的整体生理和毒力产生深远影响。机会致病菌铜绿假单胞菌能够定植于囊性纤维化（CF）个体的呼吸道，在那里它经历进化以优化作为持久慢性人类定植者的生存。在存在人呼吸道粘液的情况下细菌生长后，测定来自CF患者的宿主适应性藻酸盐过量产生分离株的转录组。这种稳定的粘液菌株响应于来自粘液的许多调节输入，导致藻酸盐生产的意外抑制。培养基中的粘液还诱导过氧化氢酶和额外的过氧化物解毒酶的产生，并引起能量产生途径的重组。一个特定的抗菌VI型分泌系统也诱导粘液生长的细胞。最后，鉴定了一组小的调节RNA，其中一部分是粘液调节的。这份报告提供了一个快照的反应，在病原体适应人类宿主通过同化的调节信号，从组织，优化其长期生存的潜力。囊性纤维化（CF）患者的慢性定植的基础上的机会致病菌铜绿假单胞菌继续代表一个具有挑战性的问题，为基础的科学家和临床医生。在这项研究中，宿主适应，藻酸盐过量生产铜绿假单胞菌2192菌株被用来评估其转录水平的变化后，在呼吸道CF粘液的生长。取得了几个重大和出乎意料的发现：（i）尽管菌株2192中藻酸盐的过量生产是由稳定突变引起的，但粘液来源的信号引起藻酸盐生物合成基因的转录水平的降低;（ii）粘液激活VI型分泌系统的表达，这是杀死混合群体中其他细菌的机制;（iii）呼吸相关基因的表达发生了改变;（iv）鉴定了几种小的调节RNA，其中一些是粘液调节的。这项工作突出了宿主环境在塑造细菌生存策略方面的强烈影响。
Adaptation of bacterial pathogens to a host can lead to the selection and accumulation of specific mutations in their genomes with profound effects on the overall physiology and virulence of the organisms. The opportunistic pathogen Pseudomonas aeruginosa is capable of colonizing the respiratory tract of individuals with cystic fibrosis (CF), where it undergoes evolution to optimize survival as a persistent chronic human colonizer. The transcriptome of a host-adapted, alginate-overproducing isolate from a CF patient was determined following growth of the bacteria in the presence of human respiratory mucus. This stable mucoid strain responded to a number of regulatory inputs from the mucus, resulting in an unexpected repression of alginate production. Mucus in the medium also induced the production of catalases and additional peroxide-detoxifying enzymes and caused reorganization of pathways of energy generation. A specific antibacterial type VI secretion system was also induced in mucus-grown cells. Finally, a group of small regulatory RNAs was identified and a fraction of these were mucus regulated. This report provides a snapshot of responses in a pathogen adapted to a human host through assimilation of regulatory signals from tissues, optimizing its long-term survival potential. The basis for chronic colonization of patients with cystic fibrosis (CF) by the opportunistic pathogen Pseudomonas aeruginosa continues to represent a challenging problem for basic scientists and clinicians. In this study, the host-adapted, alginate-overproducing Pseudomonas aeruginosa 2192 strain was used to assess the changes in its transcript levels following growth in respiratory CF mucus. Several significant and unexpected discoveries were made: (i) although the alginate overproduction in strain 2192 was caused by a stable mutation, a mucus-derived signal caused reduction in the transcript levels of alginate biosynthetic genes; (ii) mucus activated the expression of the type VI secretion system, a mechanism for killing of other bacteria in a mixed population; (iii) expression of a number of genes involved in respiration was altered; and (iv) several small regulatory RNAs were identified, some being mucus regulated. This work highlights the strong influence of the host environment in shaping bacterial survival strategies.