Nematode Peptides with Host-Directed Anti-inflammatory Activity Rescue Caenorhabditis elegans from a Burkholderia pseudomallei Infection.
Nematode Peptides with Host-Directed Anti-inflammatory Activity Rescue Caenorhabditis elegans from a Burkholderia pseudomallei Infection.
复制标题
DOI：
10.3389/fmicb.2016.01436
复制
发表时间：
2016
影响因子：
5.2
通讯作者：
Nathan S
中科院分区：
文献类型：
--
作者：
Lim MP;Firdaus-Raih M;Nathan S
类鼻疽伯克霍尔德氏菌是类鼻疽病的病原体，是越来越多的抗生素耐药性越来越强的细菌病原体之一。抗菌肽（AMP）已被研究作为治疗微生物感染的替代方法，因为通常，病原体将对AMP产生抗性的可能性较低。在这项研究中，36个候选秀丽隐杆线虫基因，编码分泌肽<150个氨基酸，以前被证明在感染过程中过表达的B。从感染线虫的表达谱中鉴定出pseudomallei。基于RNA干扰（RNAi）的12/34肽编码基因的敲低导致线虫对B的易感性增强。假鼻疽而不影响蠕虫适应性。微量稀释试验表明，两种肽NLP-31和Y43C5A.3表现出抗B。假鼻疽活性以剂量依赖性的方式对不同的病原体。时间杀灭分析表明，这些肽对B有抑菌作用。浓度高达8× MIC 90时的鼻疽假单胞菌。SYTOX绿色试验证明NLP-31和Y 43 C5A.3不会破坏B。假鼻疽膜相反，凝胶阻滞试验表明，这两种肽能够结合DNA和干扰细菌的活力。同时，显微镜检查显示NLP-31和Y43C5A.3处理的细胞诱导细胞凋亡，这是DNA合成抑制的标志。此外，这些肽还调节B中炎性细胞因子的表达。类鼻疽感染巨噬细胞。总的来说，这些发现证明了NLP-31和Y43C5A.3作为抗B的潜力。基于其作为免疫调节剂的功能的类鼻疽肽。
Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs) have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi)-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8× MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators.
登录
查看更多内容
影响因子：
7.3
作者：
BESSALLE, R;GOREA, A;FRIDKIN, M
通讯作者：
FRIDKIN, M
影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
Barton GJ
影响因子：
4.9
作者：
Burtnick, MN;Woods, DE
通讯作者：
Woods, DE
影响因子：
5.8
作者：
Gautier, Romain;Douguet, Dominique;Drin, Guillaume
通讯作者：
Drin, Guillaume
影响因子：
2.2
作者：
Herigstad, B;Hamilton, M;Heersink, J
通讯作者：
Heersink, J