Foik Ilona P, Shu Runhang, Abbondante Serena, Kasallis Summer J, Urban Lauren A, Huang Andy P, Duong Leora, Marshall Michaela E, Pearlman Eric, Downing Timothy L, Siryaporn Albert
Department of Physics & Astronomy, University of California Irvine, USA.
Institute of Physical Chemistry, Polish Academy of Sciences, Poland.
bioRxiv. 2025 May 23:2022.02.01.478687. doi: 10.1101/2022.02.01.478687.
Neutrophils respond to the presence of bacteria by producing oxidative molecules that are lethal to bacteria, including hypochlorous acid (HOCl). However, the extent to which bacteria detect activated neutrophils or the HOCl that neutrophils produce, has not been understood. Here we report that the opportunistic bacterial pathogen upregulates expression of its operon in response to stimulated neutrophils. This operon was previously shown to be activated by shear rate of fluid flow in the environment. We show that is specifically upregulated by HOCl, while other oxidative factors that neutrophils produce including HO, do not upregulate . The -dependent response to HOCl upregulates the expression of multiple methionine sulfoxide reductases, which relieve oxidative stress that would otherwise inhibit growth. Our findings suggest a model in which the detection of shear rate or HOCl activates the operon, which serves as an early and sensitive host-detection system for that improves its own survival against neutrophil-mediated host defenses. In support of this model, we found that the operon is activated in an infection model where flow and neutrophils are present. This response could promote the bacterium's pathogenicity, colonization of tissue, and persistence in infections.
中性粒细胞通过产生对细菌具有致死性的氧化分子(包括次氯酸(HOCl))来应对细菌的存在。然而,细菌检测活化中性粒细胞或中性粒细胞产生的HOCl的程度尚不清楚。在此,我们报告机会性细菌病原体在响应受刺激的中性粒细胞时会上调其操纵子的表达。该操纵子先前已被证明可被环境中流体流动的剪切速率激活。我们表明, 是由HOCl特异性上调的,而中性粒细胞产生的其他氧化因子(包括HO)不会上调 。对HOCl的 依赖性反应上调了多种甲硫氨酸亚砜还原酶的表达,这些酶可减轻否则会抑制生长的氧化应激。我们的研究结果提出了一种模型,其中剪切速率或HOCl的检测激活了 操纵子,该操纵子作为 的早期和敏感的宿主检测系统,可提高其自身抵抗中性粒细胞介导的宿主防御的生存能力。为支持该模型,我们发现在存在流动和中性粒细胞的感染模型中 操纵子被激活。这种反应可能会促进细菌的致病性、组织定植和感染中的持续存在。