Exogenous maltose enhances Zebrafish immunity to levofloxacin-resistant Vibrio alginolyticus
Exogenous maltose enhances Zebrafish immunity to levofloxacin-resistant Vibrio alginolyticus
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外源麦芽糖增强斑马鱼对左氧氟沙星耐药弧菌的免疫力
DOI：
10.1111/1751-7915.13582
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发表时间：
2020-05-04
影响因子：
5.7
通讯作者：
Peng, Bo
中科院分区：
文献类型：
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作者：
Jiang, Ming;Yang, Lifen;Peng, Bo
了解细菌适应性、抗生素耐药性、宿主免疫力和宿主代谢之间的相互作用，有助于指导治疗并提高针对耐药病原体的免疫力。获得左氧氟沙星（Lev）耐药性会影响溶藻弧菌在体外和体内的适应性。与左氧氟沙星敏感（Lev - S）的溶藻弧菌相比，左氧氟沙星耐药（Lev - R）的溶藻弧菌生长缓慢、致病性降低，且对宿主斑马鱼（Danio rerio）的杀伤具有更强的抵抗力，这表明Lev - R溶藻弧菌在斑马鱼中引发的先天免疫反应比Lev - S溶藻弧菌更弱。在感染Lev - S或Lev - R溶藻弧菌的斑马鱼代谢组中检测到了差异。麦芽糖作为一种关键代谢物，在感染Lev - R溶藻弧菌的斑马鱼体内显著下调，而外源性麦芽糖可增强斑马鱼对Lev - R溶藻弧菌的免疫反应，从而更好地清除感染。此外，我们证明外源性麦芽糖可刺激宿主产生溶菌酶，并促使溶菌酶与Lev - R溶藻弧菌结合，这一过程依赖于细菌的膜电位。我们认为，外源接触关键代谢物可能是治疗和/或控制耐药细菌感染的一种有效策略。
Understanding the interplay between bacterial fitness, antibiotic resistance, host immunity and host metabolism could guide treatment and improve immunity against antibiotic-resistant pathogens. The acquisition of levofloxacin (Lev) resistance affects the fitness of Vibrio alginolyticus in vitro and in vivo. Lev-resistant (Lev-R) V. alginolyticus exhibits slow growth, reduced pathogenicity and greater resistance to killing by the host, Danio rerio (zebrafish), than Lev-sensitive (Lev-S) V. alginolyticus, suggesting that Lev-R V. alginolyticus triggers a weaker innate immune response in D. rerio than Lev-S V. alginolyticus. Differences were detected in the metabolome of D. rerio infected with Lev-S or Lev-R V. alginolyticus. Maltose, a crucial metabolite, is significantly downregulated in D. rerio infected with Lev-R V. alginolyticus, and exogenous maltose enhances the immune response of D. rerio to Lev-R V. alginolyticus, leading to better clearance of the infection. Furthermore, we demonstrate that exogenous maltose stimulates the host production of lysozyme and its binding to Lev-R V. alginolyticus, which depends on bacterial membrane potential. We suggest that exogenous exposure to crucial metabolites could be an effective strategy for treating and/or managing infections with antibiotic-resistant bacteria.