Congener-Induced Sulfur-Related Metabolism Interference Therapy Promoted by Photothermal Sensitization for Combating Bacteria
Congener-Induced Sulfur-Related Metabolism Interference Therapy Promoted by Photothermal Sensitization for Combating Bacteria
复制标题
光热敏化促进同系物诱导的硫相关代谢干扰疗法对抗细菌
DOI：
10.1002/adma.202104410
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发表时间：
2021-09-05
影响因子：
29.4
通讯作者：
Zhang, Xianlong
中科院分区：
文献类型：
--
作者：
He, Renke;Ding, Cheng;Zhang, Xianlong
代谢稳态对于单个细胞保持存活至关重要。更强的代谢稳态允许细菌在体内存活并对宿主造成持续伤害，这在生物膜干预的植入物相关感染（IAI）中尤其典型。基于硒（Se）和硫（S）作为同源物在细菌代谢中的竞争作用，提出了同源物诱导的硫相关代谢干扰疗法（SMIT），通过特异性破坏细菌代谢稳态来消除IAI。最初的纳米药物二硒化锰（MnSe2）被设计为在细菌中产生可渗透的H2Se，由酸性微环境触发。H2Se是H2S的同源替代物，作为细菌特异性的中间代谢产物，可以嵌入到细菌的H2S利用途径中，进而干扰细菌内下游硫相关代谢状态。蛋白质组学研究表明，SMIT后核糖体相关蛋白表达严重下调，基本代谢途径主要发生紊乱，揭示了SMIT对细菌代谢稳态的破坏。通过蛋白质组学研究和体外和体内抗IAI效应验证，通过MnSe2纳米颗粒的光热处理（PTT）提供的温和温度敏化，SMIT的效率显著提高。与智能纳米药物，PTT促进SMIT策略对IAI提供了一个新的见解，对代谢稳态的干扰设计与生化相似性证明。
Metabolic homeostasis is vital for individual cells to keep alive. Stronger metabolic homeostasis allows bacteria to survive in vivo and do persistent harm to hosts, which is especially typical in implant-associated infection (IAI) with biofilm intervention. Herein, based on the competitive role of selenium (Se) and sulfur (S) in bacteria metabolism as congeners, a congener-induced sulfur-related metabolism interference therapy (SMIT) eradicating IAI is proposed by specific destruction of bacteria metabolic homeostasis. The original nanodrug manganese diselenide (MnSe2) is devised to generate permeable H2Se in bacteria, triggered by the acidic microenvironment. H2Se, the congener substitution of H2S, as a bacteria-specific intermediate metabolite, can embed itself into the H2S-utilization pathway and further alternatively disrupt the downstream sulfur-related metabolism state inside bacteria. A proteomic study indicates ribosome-related proteins are heavily downregulated and the basic metabolic pathways are mainly disordered after SMIT, revealing the destruction of bacteria metabolic homeostasis. The efficiency of SMIT is significantly promoted with the mild temperature sensitization provided by the photothermal treatment (PTT) of MnSe2 nanoparticles, verified by the proteomic study and the anti-IAI effect in vitro and in vivo. With the intelligent nanodrug, a PTT-promoted SMIT strategy against IAI is provided and a new insight into the interference design toward metabolic homeostasis with biochemical similarity is demonstrated.