Rufomycin Exhibits Dual Effects Against Mycobacterium abscessus Infection by Inducing Host Defense and Antimicrobial Activities.
Rufomycin Exhibits Dual Effects Against Mycobacterium abscessus Infection by Inducing Host Defense and Antimicrobial Activities.
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DOI：
10.3389/fmicb.2021.695024
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发表时间：
2021
影响因子：
5.2
通讯作者：
Jo EK
中科院分区：
文献类型：
--
作者：
Park CR;Paik S;Kim YJ;Kim JK;Jeon SM;Lee SH;Whang J;Cheng J;Suh JW;Cao J;Shetye G;Chen SN;McAlpine J;Pauli GF;Franzblau S;Cho S;Jo EK
非结核分枝杆菌肺部感染往往由于抗生素耐药性问题而加重。需要开发诱导宿主免疫应答和抗微生物活性的新药。这项研究表明，红霉素4/5/6/7（红霉素4-7），其目标ClpC 1作为一个亚基的酪蛋白溶解蛋白复合物ClpC 1/ClpP 1/ClpP 2的分枝杆菌，表现出双重作用，在宿主先天防御和体内抗微生物活性对粗糙形态型的分枝杆菌（Mabs-R），临床严重的形态型，导致过度炎症。在体内和巨噬细胞中，红霉素4-7处理显示出抗Mab肺部感染的抗菌作用。此外，红霉素4-7显著降低炎症，但通过上调转录因子EB（TFEB）的核转位增强自噬/溶酶体基因。此外，在Mabs-R感染期间，红霉素4-7处理有效地抑制了巨噬细胞中的线粒体损伤和氧化应激。总的来说，红霉素4-7介导的诱导抗微生物活性和宿主免疫防御的双重作用可能赋予针对Mabs-R感染的治疗优势。
Nontuberculous mycobacterial pulmonary infection is often aggravated due to antibiotic resistance issues. There is a need for development of new drugs inducing both host immune responses and antimicrobial activities. This study shows that the rufomycins 4/5/6/7 (Rufomycin 4–7), which targets ClpC1 as a subunit of caseinolytic protein complex ClpC1/ClpP1/ClpP2 of mycobacteria, exhibits a dual effect in host innate defense and in vivo antimicrobial activities against a rough morphotype of Mycobacterium abscessus (Mabs-R), a clinically severe morphotype that causes hyperinflammation. Rufomycin 4–7 treatment showed antimicrobial effects against Mabs pulmonary infection in vivo and in macrophages. In addition, Rufomycin 4–7 significantly decreased inflammation, but enhanced the autophagy/lysosomal genes through upregulation of the nuclear translocation of transcription factor EB (TFEB). Furthermore, Rufomycin 4–7 treatment effectively inhibited mitochondrial damage and oxidative stresses in macrophages during Mabs-R infection. Collectively, Rufomycin 4–7-mediated dual effects inducing both antimicrobial activities and host immune defense might confer an advantage to treatment against Mabs-R infection.
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影响因子：
3.7
作者：
Caverly LJ;Caceres SM;Fratelli C;Happoldt C;Kidwell KM;Malcolm KC;Nick JA;Nichols DP
通讯作者：
Nichols DP
影响因子：
13.3
作者：
Kim, Tae Sung;Jin, Yeung Bae;Jo, Eun-Kyeong
通讯作者：
Jo, Eun-Kyeong
DOI：
10.1007/5584_2016_45
发表时间：
2017-01-01
期刊：
RESPIRATORY TREATMENT AND PREVENTION
影响因子：
--
作者：
Porvaznik, I.;Solovic, I.;Mokry, J.
通讯作者：
Mokry, J.
影响因子：
9.1
作者：
Kim TS;Kim YS;Yoo H;Park YK;Jo EK
通讯作者：
Jo EK
影响因子：
4.4
作者：
Kim, Yi Sak;Lee, Hye-Mi;Jo, Eun-Kyeong
通讯作者：
Jo, Eun-Kyeong