Zhou Yong-Hui, Xu Chang-Geng, Yang Yan-Bei, Xing Xiao-Xu, Liu Xin, Qu Qian-Wei, Ding Wen-Ya, Bello-Onaghise God'spower, Li Yan-Hua
College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin, China.
Front Microbiol. 2018 Apr 5;9:665. doi: 10.3389/fmicb.2018.00665. eCollection 2018.
() is an AT-rich and coagulase-negative (CNS). It is normally regarded as non-pathogenic, however, recent studies have demonstrated that it is related to human opportunistic infections and bovine mastitis. In addition, strains have the ability to form biofilm. Biofilms are also involved in chronic infections and antibiotic resistance, there are only a few reports about cefquinome inhibiting biofilm formation and the protein targets of cefquinome. In our study, we found that sub-MICs of cefquinome were sufficient to inhibit biofilm formation. To investigate the potential protein targets of cefquinome, we used iTRAQ for the analyses of cells at two different conditions: 1/2-MIC (0.125 μg/mL) cefquinome treatment and no treatment. Using iTRAQ technique and KEGG database analysis, we found that proteins differently expression in histidine metabolism pathway may play a role in the process by which 1/2-MIC (0.125 μg/mL) cefquinome inhibits biofilm formation. Interestingly, we found a sharply down-regulated enzyme [A0A068E9J3 imidazoleglycerol-phosphate dehydratase (IGPD)] involved in histidine metabolism pathway in cefquinome-treated cells. We demonstrated the important role of IGPD in sub-MICs cefquinome inhibiting biofilm formation of by gene () knockout, IGPD enzyme activity and histidine content assays. Thus, our data sheds light on important role of histidine metabolism in biofilm formation; especially, IGPD involved in histidine metabolism might play a crucial role in sub-MICs cefquinome inhibition of biofilm formation of , and we propose IGPD as an attractive protein target of cefquinome.
(某菌)是一种富含AT且凝固酶阴性的(中枢神经系统相关菌)。它通常被认为是非致病性的,然而,最近的研究表明它与人类机会性感染和牛乳腺炎有关。此外,该菌株具有形成生物膜的能力。生物膜也与慢性感染和抗生素耐药性有关,关于头孢喹肟抑制生物膜形成及其蛋白质靶点的报道较少。在我们的研究中,我们发现头孢喹肟的亚抑菌浓度足以抑制生物膜形成。为了研究头孢喹肟的潜在蛋白质靶点,我们使用iTRAQ对处于两种不同条件的细胞进行分析:1/2-MIC(0.125μg/mL)头孢喹肟处理和未处理。通过iTRAQ技术和KEGG数据库分析,我们发现组氨酸代谢途径中差异表达的蛋白质可能在1/2-MIC(0.125μg/mL)头孢喹肟抑制生物膜形成的过程中起作用。有趣的是,我们发现头孢喹肟处理的细胞中参与组氨酸代谢途径的一种酶[A0A068E9J3咪唑甘油磷酸脱水酶(IGPD)]急剧下调。我们通过基因(某基因)敲除、IGPD酶活性和组氨酸含量测定证明了IGPD在亚抑菌浓度头孢喹肟抑制(某菌)生物膜形成中的重要作用。因此,我们的数据揭示了组氨酸代谢在(某菌)生物膜形成中的重要作用;特别是,参与组氨酸代谢的IGPD可能在亚抑菌浓度头孢喹肟抑制(某菌)生物膜形成中起关键作用,并且我们提出IGPD作为头孢喹肟有吸引力的蛋白质靶点。