Importance of Polyphosphate Kinase 1 for Campylobacter jejuni Viable-but-Nonculturable Cell Formation, Natural Transformation, and Antimicrobial Resistance
Importance of Polyphosphate Kinase 1 for Campylobacter jejuni Viable-but-Nonculturable Cell Formation, Natural Transformation, and Antimicrobial Resistance
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DOI：
10.1128/aem.01603-09
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发表时间：
2009-12-15
影响因子：
4.4
通讯作者：
Rajashekara, Gireesh
中科院分区：
文献类型：
--
作者：
Gangaiah, Dharanesh;Kassem, Issmat I.;Rajashekara, Gireesh
空肠弯曲杆菌是一种革兰氏阴性的嗜微气细菌，是人类细菌性肠胃炎的主要病因。虽然被认为是脆弱和挑剔的，缺乏许多经典的应激反应机制，但空肠梭菌表现出非凡的生存和适应能力，成功地感染了人类并在环境中持续存在。因此，了解空肠梭菌生存和适应各种应激条件的生理和遗传特性对治疗干预至关重要。重要的是多磷酸激酶1 (PPK1)，它是介导多磷酸合成的关键酶，是许多细菌生存、介导应激反应、宿主定植和毒力的必需分子。因此，我们研究了PPK1在空肠c的发病机制、应激生存和适应中的作用。我们的研究结果表明，空肠C. Delta ppk1突变体缺乏聚磷积累，这与酸胁迫下形成存活但不可培养的细胞的能力下降有关。Delta ppk1突变体也表现出自然转化频率降低和对各种抗菌素的易感性增加。此外，Delta ppk1突变体在鸡的定植中表现出剂量依赖性缺陷。Delta ppk1突变体与野生型ppk1拷贝的互补将缺陷表型恢复到与野生型相似的水平。这些结果表明poly-P在空肠梭菌的逆境生存和适应中起着重要作用，可能与基因组可塑性和耐药性的传播和发展有关。这些发现突出了PPK1作为治疗干预新靶点的潜力。
Campylobacter jejuni, a gram-negative, microaerophilic bacterium, is a predominant cause of bacterial gastroenteritis in humans. Although considered fragile and fastidious and lacking many classical stress response mechanisms, C. jejuni exhibits a remarkable capacity for survival and adaptation, successfully infecting humans and persisting in the environment. Consequently, understanding the physiological and genetic properties that allow C. jejuni to survive and adapt to various stress conditions is crucial for therapeutic interventions. Of importance is polyphosphate (poly-P) kinase 1 (PPK1), which is a key enzyme mediating the synthesis of poly-P, an essential molecule for survival, mediating stress responses, host colonization, and virulence in many bacteria. Therefore, we investigated the role of PPK1 in C. jejuni pathogenesis, stress survival, and adaptation. Our findings demonstrate that a C. jejuni Delta ppk1 mutant was deficient in poly-P accumulation, which was associated with a decreased ability to form viable-but-nonculturable cells under acid stress. The Delta ppk1 mutant also showed a decreased frequency of natural transformation and an increased susceptibility to various antimicrobials. Furthermore, the Delta ppk1 mutant was characterized by a dose-dependent deficiency in chicken colonization. Complementation of the Delta ppk1 mutant with the wild-type copy of ppk1 restored the deficient phenotypes to levels similar to those of the wild type. Our results suggest that poly-P plays an important role in stress survival and adaptation and might contribute to genome plasticity and the spread and development of antimicrobial resistance in C. jejuni. These findings highlight the potential of PPK1 as a novel target for therapeutic interventions.