Decreased Expression of Type 1 Fimbriae by a pst Mutant of Uropathogenic Escherichia coli Reduces Urinary Tract Infection
Decreased Expression of Type 1 Fimbriae by a pst Mutant of Uropathogenic Escherichia coli Reduces Urinary Tract Infection
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DOI：
10.1128/iai.00162-12
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发表时间：
2012-08-01
影响因子：
3.1
通讯作者：
Dozois, Charles M.
中科院分区：
文献类型：
--
作者：
Crepin, Sebastien;Houle, Sebastien;Dozois, Charles M.
pstSCAB-phoU操纵子编码磷酸盐特异性转运系统（Pst）。Pst的缺失组成性激活Pho调节子并降低细菌毒力。然而，通过灭活Pst降低细菌毒力的具体机制知之甚少。在尿路致病性大肠杆菌（UPEC）菌株CFT 073中，PST的灭活降低了CBA/J小鼠的尿路定植。的PST突变体是缺乏1型菌毛的生产，并表现出减少的fimA结构基因的表达与差异表达的fimB，fimE，ipuA，和ipbA基因，编码重组酶，介导的fim启动子倒位。使用fim锁相衍生物证实了fim下调在pst突变体减毒中的作用，这证明了毒力的显著增加。此外，pst突变体侵袭人膀胱上皮细胞的能力较低。由于1型菌毛通过促进膀胱细胞的定殖和侵袭而有助于UPEC毒力，因此由pst突变体引起的膀胱定殖减少主要归因于这些菌毛的下调。阐明通过激活UPEC中的Pho调节子介导1型菌毛控制的机制可能为尿路感染的治疗或药物治疗开辟新的途径。
The pstSCAB-phoU operon encodes the phosphate-specific transport system (Pst). Loss of Pst constitutively activates the Pho regulon and decreases bacterial virulence. However, specific mechanisms underlying decreased bacterial virulence through inactivation of Pst are poorly understood. In uropathogenic Escherichia coli (UPEC) strain CFT073, inactivation of pst decreased urinary tract colonization in CBA/J mice. The pst mutant was deficient in production of type 1 fimbriae and showed decreased expression of the fimA structural gene which correlated with differential expression of the fimB, fimE, ipuA, and ipbA genes, encoding recombinases, mediating inversion of the fim promoter. The role of fim downregulation in attenuation of the pst mutant was confirmed using a fim phase-locked-on derivative, which demonstrated a significant gain in virulence. In addition, the pst mutant was less able to invade human bladder epithelial cells. Since type 1 fimbriae contribute to UPEC virulence by promoting colonization and invasion of bladder cells, the reduced bladder colonization by the pst mutant is predominantly attributed to downregulation of these fimbriae. Elucidation of mechanisms mediating the control of type 1 fimbriae through activation of the Pho regulon in UPEC may open new avenues for therapeutics or prophylactics against urinary tract infections.