Mucoid Pseudomonas aeruginosa in cystic fibrosis: Characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection
Mucoid Pseudomonas aeruginosa in cystic fibrosis: Characterization of muc mutations in clinical isolates and analysis of clearance in a mouse model of respiratory infection
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DOI：
10.1128/iai.65.9.3838-3846.1997
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发表时间：
1997-09-01
影响因子：
3.1
通讯作者：
Deretic, V
中科院分区：
文献类型：
--
作者：
Boucher, JC;Mudd, HYMH;Deretic, V
来自囊性纤维化（CF）患者的铜绿假单胞菌分离物的区别特征是它们的粘液样、外泌多糖藻酸盐过量产生表型。转化为粘液样的一种机制是基于algU mucABCD簇中的突变，其编码应激因子AlgU及其调节因子。然而，在实验室菌株中转化为粘液样可以通过其他染色体位点中的突变来实现。我们通过分析来自53名CF患者的粘液样铜绿假单胞菌分离物的集合中的mucA的状态，研究了粘液样铜绿假单胞菌在CF中出现的机制。当在实验室条件下失活时，这种algU的负调节因子导致转化为粘液性。粘液样CF分离物中mucA改变的总频率为84%，核苷酸序列分析显示，大多数改变导致mucA编码序列的提前终止。来自三名CF患者的成对非粘液样和粘液样铜绿假单胞菌分离物的比较表明仅在粘液样菌株中存在mucA突变。有趣的是，来自尿路感染的粘液样铜绿假单胞菌分离物也在mucA基因中具有突变，在气溶胶感染模型中，用C57 BL/6 J、BALB/c和DBA/2NHsd小鼠研究了CF分离物从鼠肺中的清除。基于它们的藻酸盐产生对培养基中盐浓度的依赖性，选择两种CF菌株用于进一步研究，用于检查粘液性对肺清除率的影响。在大多数测试的小鼠品系中观察到，相对于非粘液细菌，活粘液铜绿假单胞菌细胞从鼠肺的回收率有统计学显著改善。总的来说，本文报道的结果表明，mucA最可能是CF中转化为粘体的优先位点，并且mucA突变型铜绿假单胞菌中藻酸盐的过量产生提高了其对肺中先天清除机制的抗性。
A distinguishing feature of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients is their mucoid, exopolysaccharide alginate-overproducing phenotype, One mechanism of conversion to mucoidy is based on mutations in the algU mucABCD cluster, encoding the stress a factor AlgU and its regulators, However, conversion to mucoidy in laboratory strains can be achieved via mutations in other chromosomal sites, Here, we investigated mechanisms of the emergence of mucoid P. aeruginosa in CF by analyzing the status of mucA in a collection of mucoid P. aeruginosa isolates from 53 CF patients, This negative regulator of algU, when inactivated under laboratory conditions, causes conversion to mucoidy, The overall frequency of mucA alterations in mucoid CF isolates was 84%, Nucleotide sequence analyses revealed that the majority of the alterations caused premature termination of the mucA coding sequence, Comparison of paired nonmucoid and mucoid P. aeruginosa isolates from three CF patients indicated the presence of mucA mutations only in the mucoid strains, Interestingly, mucoid P. aeruginosa isolates from urinary tract infections also had mutations in the mucA gene, Clearance of CF isolates from the murine lung was investigated in an aerosol infection model with C57BL/6J, BALB/c, and DBA/2NHsd mice, Two CF strains, selected for further study based on the dependence of their alginate production on the concentration of salt in the medium, were used to examine the effects of mucoidy on pulmonary clearance, Statistically significant improvement in recovery from the murine lung of viable mucoid P. aeruginosa cells relative to the nonmucoid bacteria was observed in the majority of mouse strains tested, Collectively, the results reported here suggest that mucA is most likely the preferential site for conversion to mucoidy in CF and that alginate overproduction in mucA-mutant P. aeruginosa improves its resistance to the innate clearance mechanisms in the lung.