Pathoadaptive Alteration of Salmonella Biofilm Formation in Response to the Gallbladder Environment.
Pathoadaptive Alteration of Salmonella Biofilm Formation in Response to the Gallbladder Environment.
复制标题
沙门氏菌生物膜形成响应胆囊环境的病理适应性改变。
DOI：
10.1128/jb.00774-18
复制
发表时间：
2019
影响因子：
3.2
通讯作者：
Gunn,JohnS
中科院分区：
文献类型：
--
作者：
Neiger,MichaelR;González,JuanF;Gonzalez-Escobedo,Geoffrey;Kuck,Harkness;White,Peter;Gunn,JohnS
伤寒是一种人类特有的疾病，主要由伤寒沙门氏菌引起。据估计，3%至5%的伤寒感染者成为慢性带菌者。研究表明，慢性携带的机制涉及胆结石表面上的生物膜形成。在先前使用慢性携带小鼠模型的研究过程中，从小鼠胆结石中回收了肠道沙门氏菌血清型鼠伤寒沙门氏菌分离株，其生物膜形成比野生型增加2倍。为了鉴定导致表型的基因，测定并比较了该分离株和其他分离株的基因组序列。这些序列鉴定了14个基因的单核苷酸多态性（SNP）。在最有希望的候选人envZandrcsB中产生了突变，但无论是单独还是组合，都没有显示出增加的生物膜形成能力。然而，hyperbiofilm分离物确实存在使用不同技术观察到的细胞附属物的变化和与胆固醇的优先结合。还检查了分离株的全身毒力和在慢性感染小鼠模型中定殖胆囊/胆结石的能力，证明了全身毒力缺陷和胆囊/胆结石定殖减少。最后，为了确定超生物膜分离株的出现是否可以在体外复制，以及这是否是一个常见的事件，野生型沙门氏菌属。在模拟胆囊的条件下在体外长时间生长，导致高比例的分离株复制了原始分离株的超生物膜表型。因此，Salmonellaspp。在胆囊/胆囊模拟条件下获得随机突变，这可能有助于持续存在，但对全身毒力产生负面影响。重要信息慢性携带者是伤寒在地方性地区传播的主要宿主。伤寒沙门氏菌在胆结石上形成生物膜以持续存在。经过9个月的慢性携带小鼠研究，恢复了具有增强生物膜形成能力的菌株。在对该菌株进行测序并重新产生一些突变后，我们无法复制表型。分离物确实显示出鞭毛的差异，偏好与胆固醇结合，以及系统性毒力缺陷。最后，在体外模拟胆囊条件。60天后，当存在胆结石时，超生物膜分离物增加了4.5倍。这些结果表明，Salmonellaspp.可以经历遗传变化，改善胆囊中的持久性，尽管代价是降低毒力。
Typhoid fever, a human-specific disease, is primarily caused by the pathogen Salmonella enterica serovar Typhi. It is estimated that 3 to 5% of people infected with typhoid fever become chronic carriers. Studies have demonstrated that a mechanism of chronic carriage involves biofilm formation on gallstone surfaces. In the course of a previous study using a chronic carriage mouse model, a Salmonella enterica serovar Typhimurium isolate was recovered from a mouse gallstone that exhibited a 2-fold increase in biofilm formation over the wild type. In order to identify the gene(s) responsible for the phenotype, the genomic sequences of this isolate and others were determined and compared. These sequences identified single nucleotide polymorphisms (SNPs) in 14 genes. Mutations in the most promising candidates,envZandrcsB,were created, but neither showed increased biofilm-forming ability separately or in combination. The hyperbiofilm isolate did, however, present variations in cellular appendages observable using different techniques and a preferential binding to cholesterol. The isolate was also examined for systemic virulence and the ability to colonize the gallbladder/gallstones in a mouse model of chronic infection, demonstrating a systemic virulence defect and decreased gallbladder/gallstone colonization. Finally, to determine if the appearance of hyperbiofilm isolates could be replicatedin vitroand if this was a common event, wild-type Salmonella spp. were grown long termin vitrounder gallbladder-mimicking conditions, resulting in a high proportion of isolates that replicated the hyperbiofilm phenotype of the original isolate. Thus,Salmonellaspp. acquire random mutations under the gallbladder/gallbladder-simulating conditions that may aid persistence but negatively affect systemic virulence.IMPORTANCEChronic carriers are the main reservoirs for the spread of typhoid fever in regions of endemicity.SalmonellaTyphi forms biofilms on gallstones in order to persist. A strain with enhanced biofilm-forming ability was recovered after a nine-month chronic-carriage mouse study. After sequencing this strain and recreating some of the mutations, we could not duplicate the phenotype. The isolate did show a difference in flagella, a preference to bind to cholesterol, and a systemic virulence defect. Finally, gallbladder conditions were simulatedin vitro. After 60 days, there was a 4.5-fold increase in hyperbiofilm isolates when a gallstone was present. These results indicate thatSalmonellaspp. can undergo genetic changes that improve persistence in gallbladder albeit at the cost of decreased virulence.