Quorum-sensing regulator LsrR modulates avian pathogenic Escherichia coli pathogenicity through direct regulation of cysN
文献类型: 外文期刊
作者: Nawaz, Saqib;Wang, Zhihao;Jiang, Wei;Kong, Lanfang;Yin, Huifang;Bao, Yinli;Huang, Cuiqin;Chen, Zhaoguo;Zhang, Yan;Han, Xiangan
作者机构:
关键词: virulence regulation;sulfur metabolism;immune evasion;efflux pumps;host-pathogen interaction
期刊名称: INFECTION AND IMMUNITY
ISSN: 0019-9567
年卷期: 2025 年
页码:
收录情况: SCIE(2025版)
摘要: Avian Pathogenic Escherichia coli (APEC) is a major cause of economic loss in poultry, exacerbated by the rising prevalence of antibiotic resistance. While sulfur metabolism is essential for bacterial growth, its specific role and regulation in APEC virulence remain poorly understood. This study identifies the LsrR-cysN axis as a novel regulatory pathway that critically governs APEC virulence. We demonstrate that the quorum-sensing regulator LsrR directly binds to the cysN promoter, activating its transcription. Functional analysis revealed that cysN deletion drastically attenuated virulence, significantly reducing biofilm formation, serum resistance, adhesion, invasion, and motility. The APEC94 triangle cysN also exhibited altered antibiotic resistance profiles, which were linked to the upregulation of efflux pumps acrA and tolC. Crucially, in a murine model, the APEC94 triangle cysN showed a 75% reduction in mortality and severe impairment in colonization of blood, lungs, liver, spleen, and kidneys. This attenuation was associated with a skewed host immune response, characterized by reduced levels of IL-2 and IL-6 and elevated levels of IL-4 and TNF-alpha. Our findings establish the LsrR-cysN axis as a central regulator connecting quorum sensing to virulence in APEC, revealing a promising target for novel anti-virulence strategies.
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