The Nutritional Environment Is Sufficient To Select Coexisting Biofilm and Quorum Sensing Mutants of Pseudomonas aeruginosa.
The Nutritional Environment Is Sufficient To Select Coexisting Biofilm and Quorum Sensing Mutants of Pseudomonas aeruginosa.
复制标题
营养环境足以选择铜绿假单胞菌共存的生物膜和群体感应突变体。
DOI：
10.1128/jb.00444-21
复制
发表时间：
2022
影响因子：
3.2
通讯作者：
Cooper,VaughnS
中科院分区：
文献类型：
--
作者：
Scribner,MichelleR;Stephens,AmeliaC;Huong,JustinL;Richardson,AnthonyR;Cooper,VaughnS
感染期间细菌种群的进化可能受到各种因素的影响，包括可用的营养物质，免疫系统和竞争微生物，从而难以确定选择进化性状的特定力量。例如，从囊性纤维化（CF）患者的气道中分离出的铜绿假单胞菌的基因组揭示了常见的突变基因，但导致其流行的表型通常是不确定的。在这里，我们专注于CF气道的营养成分对铜绿假单胞菌在良好混合（渗透压）或生物膜相关条件下生长的遗传适应的影响。在含有葡萄糖、乳酸盐和氨基酸的简单培养基中仅经过80代的实验进化后，所有的嗜酸性种群都分化成了具有CF感染常见的突变基因的谱系：莫拉A，编码生物膜形成的调节因子; orlasR，编码调节毒力因子表达的群体感应调节因子。尽管突变的群体感应通常被认为是由于毒力表型改变或社会欺骗而在体内选择的，但具有lasR突变的分离株在单独生长时表现出更高的适应性，并击败了祖先的PA 14菌株。非同义SNPs inmorA增加健身在营养浓度依赖性的方式在反硝化生长，令人惊讶的是，也增加了生物膜的生产。在生物膜条件下繁殖的种群也获得了与慢性感染相关的基因座突变，包括lasR和环二GMP调节因子roeA和wspF。这些研究结果表明，营养条件和生物膜的选择是足够的选择突变体有问题的临床表型，包括增加生物膜和改变quorum sensing. IMPORTANCEPseudomonasaeruginosa产生危险的慢性感染，是众所周知的，他们的快速多样化和administrance治疗。我们进行了进化实验，以确定适应选择的CF呼吸环境的两个具体方面：营养水平和表面附着。铜绿假单胞菌在CF气道内存在的营养物中的繁殖足以驱动多样化成在生物膜和群体感应的调节物中具有与感染期间产生的那些相同的突变的亚群。因此，机会致病菌对宿主中发现的营养物质的适应可能会选择具有使感染的治疗和清除复杂化的表型的突变体。
The evolution of bacterial populations during infections can be influenced by various factors including available nutrients, the immune system, and competing microbes, rendering it difficult to identify the specific forces that select on evolved traits. The genomes of Pseudomonas aeruginosa isolated from the airways of people with cystic fibrosis (CF), for example, have revealed commonly mutated genes, but which phenotypes led to their prevalence is often uncertain. Here, we focus on effects of nutritional components of the CF airway on genetic adaptations by P. aeruginosa grown in either well-mixed (planktonic) or biofilm-associated conditions. After only 80 generations of experimental evolution in a simple medium with glucose, lactate, and amino acids, all planktonic populations diversified into lineages with mutated genes common to CF infections:morA, encoding a regulator of biofilm formation, orlasR, encoding a quorum sensing regulator that modulates the expression of virulence factors. Although mutated quorum sensing is often thought to be selectedin vivodue to altered virulence phenotypes or social cheating, isolates withlasRmutations demonstrated increased fitness when grown alone and outcompeted the ancestral PA14 strain. Nonsynonymous SNPs inmorAincreased fitness in a nutrient concentration-dependent manner during planktonic growth and surprisingly also increased biofilm production. Populations propagated in biofilm conditions also acquired mutations in loci associated with chronic infections, includinglasRand cyclic di-GMP regulatorsroeAandwspF. These findings demonstrate that nutrient conditions and biofilm selection are sufficient to select mutants with problematic clinical phenotypes including increased biofilm and altered quorum sensing.IMPORTANCEPseudomonas aeruginosa produces dangerous chronic infections that are known for their rapid diversification and recalcitrance to treatment. We performed evolution experiments to identify adaptations selected by two specific aspects of the CF respiratory environment: nutrient levels and surface attachment. Propagation of P. aeruginosa in nutrients present within the CF airway was sufficient to drive diversification into subpopulations with identical mutations in regulators of biofilm and quorum sensing to those arising during infection. Thus, the adaptation of opportunistic pathogens to nutrients found in the host may select mutants with phenotypes that complicate treatment and clearance of infection.