Huo Caiyun, Jiao Lijiao, Li Guiping, Li Donghai, Lin Wutong, Sun Yingjian, Sun Huiling
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.
Animal Science and Technology College, Beijing University of Agriculture, Beijing, China.
Microbiol Spectr. 2023 Sep 28;11(5):e0397922. doi: 10.1128/spectrum.03979-22.
is the pathogen that causes infectious coryza, a highly contagious respiratory disease that brings a serious threat to chickens. Heme utilization systems play an important role in bacterial adversity adaptation and pathogenicity, and our previous report found the presence of heme utilization (HutZ) in . However, little is known about the function of HutZ in . In this study, the HutZ mutant strain of was successfully developed and identified by PCR and western blot analysis. Mutation of HutZ significantly retards bacterial growth under reduced iron conditions, indicating the regulatory role of HutZ on growth and iron acquisition. Notably, the HutZ mutant strain had slower growth than the wild-type strain when heme was provided as the sole source of iron; thus, HutZ is crucial for heme utilization in . Moreover, the HutZ mutant strain exhibited a markedly compromised tolerance to acid stress compared to the wild-type strain. Pathogenicity analysis showed that mutation of HutZ significantly weakened the ability of bacteria to invade and reproduce in host macrophage cells . Furthermore, the HutZ mutation could significantly decrease the bacterial virulence in chickens, which displayed lower morbidity and milder clinical symptoms. Hence, this is the first study to demonstrate in-depth the essential roles of HutZ on iron homeostasis and pathogenesis of , which provides novel insight into advances of new prophylactic vaccines against this kind of bacteria.ImportanceHeme utilization (HutZ) protein has been characterized as an important heme-degrading enzyme that is critical for the cleavage of heme to biliverdin verdoheme and can release iron to be used by bacteria. The interaction between HutZ and is still unknown. Here, we unraveled the role of HutZ on the growth, iron acquisition, heme utilization, and resistance to acidic stress in . We also uncovered the importance of HutZ for the success of infection and provided new clues to the pathogenesis strategies of this organism. This work constitutes a relevant step toward an understanding of the role of HutZ protein as a master virulence factor. Therefore, this study is of great importance for understanding the mechanisms underlying virulence and may contribute to therapeutic applications.
是引起传染性鼻炎的病原体，传染性鼻炎是一种对鸡具有高度传染性的呼吸道疾病，会给鸡带来严重威胁。血红素利用系统在细菌适应逆境和致病性方面发挥着重要作用，我们之前的报告发现中存在血红素利用蛋白（HutZ）。然而，关于HutZ在中的功能知之甚少。在本研究中，通过PCR和蛋白质免疫印迹分析成功构建并鉴定了的HutZ突变株。HutZ突变显著阻碍了细菌在低铁条件下的生长，表明HutZ对生长和铁摄取具有调节作用。值得注意的是，当以血红素作为唯一铁源时，HutZ突变株的生长比野生型菌株慢；因此，HutZ对中血红素的利用至关重要。此外，与野生型菌株相比，HutZ突变株对酸应激的耐受性明显受损。致病性分析表明，HutZ突变显著削弱了细菌在宿主巨噬细胞中侵袭和繁殖的能力。此外，HutZ突变可显著降低鸡体内的细菌毒力，鸡的发病率较低且临床症状较轻。因此，这是首次深入证明HutZ在铁稳态和致病性方面的重要作用的研究，为针对这类细菌的新型预防性疫苗的研发提供了新的见解。重要性血红素利用蛋白（HutZ）已被鉴定为一种重要的血红素降解酶，对血红素裂解为胆绿素和高铁血红素至关重要，并且可以释放铁供细菌利用。HutZ与之间的相互作用仍然未知。在这里，我们揭示了HutZ在生长、铁摄取、血红素利用和对酸性应激的抗性方面的作用。我们还发现了HutZ对感染成功的重要性，并为该生物体的致病策略提供了新线索。这项工作是理解HutZ蛋白作为主要毒力因子作用的重要一步。因此，本研究对于理解毒力的潜在机制具有重要意义，并可能有助于治疗应用。
