Conway Institute and.
Systems Biology Ireland, University College Dublin.
J Infect Dis. 2017 May 1;215(9):1459-1467. doi: 10.1093/infdis/jix139.
Our understanding of how the course of opportunistic bacterial infection is influenced by the microenvironment is limited. We demonstrate that the pathogenicity of Pseudomonas aeruginosa strains derived from acute clinical infections is higher than that of strains derived from chronic infections, where tissues are hypoxic. Exposure to hypoxia attenuated the pathogenicity of strains from acute (but not chronic) infections, implicating a role for hypoxia in regulating bacterial virulence. Mass spectrometric analysis of the secretome of P. aeruginosa derived from an acute infection revealed hypoxia-induced repression of multiple virulence factors independent of altered bacterial growth. Pseudomonas aeruginosa lacking the Pseudomonas prolyl-hydroxylase domain-containing protein, which has been implicated in bacterial oxygen sensing, displays reduced virulence factor expression. Furthermore, pharmacological hydroxylase inhibition reduces virulence factor expression and pathogenicity in a murine model of pneumonia. We hypothesize that hypoxia reduces P. aeruginosa virulence at least in part through the regulation of bacterial hydroxylases.
我们对机会性细菌感染过程如何受微环境影响的了解有限。我们证明，来源于急性临床感染的铜绿假单胞菌菌株的致病性高于来源于慢性感染（组织缺氧）的菌株。缺氧暴露会减弱来源于急性（而非慢性）感染的菌株的致病性，表明缺氧在调节细菌毒力方面发挥作用。对来源于急性感染的铜绿假单胞菌的分泌组进行质谱分析显示，缺氧诱导了多个独立于细菌生长变化的毒力因子的抑制。已被证实参与细菌氧感应的假单胞菌脯氨酰-羟化酶结构域缺失蛋白缺失的铜绿假单胞菌，其毒力因子表达减少。此外，药理学羟化酶抑制可减少肺炎小鼠模型中的毒力因子表达和致病性。我们假设，缺氧至少部分通过细菌羟化酶的调节来降低铜绿假单胞菌的毒力。
