Ramos Sónia, Chafsey Ingrid, Silva Nuno, Hébraud Michel, Santos Hugo, Capelo-Martinez José-Luis, Poeta Patrícia, Igrejas Gilberto
Institute for Biotechnology and Bioengineering, Centre for Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal; Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal; Centre for Animal and Veterinary Science, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal; Department of Veterinary Science, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
INRA (Institut National de la Recherche Agronomique), UR454 Microbiologie, Centre de Recherche de Clermont-Ferrand, F-63122 Saint-Genès Champanelle, France.
J Proteomics. 2015 Jan 15;113:378-87. doi: 10.1016/j.jprot.2014.10.012. Epub 2014 Oct 28.
Enterococci are not highly pathogenic bacteria, but the incidence of vancomycin resistance among clinical isolates of this microbial group is steadily increasing, posing a threat to public health. Vancomycin-resistant enterococci are currently some of the most recalcitrant hospital-associated pathogens against which new therapies are urgently needed. To understand the molecular mechanisms of bacterial resistance to glycopeptides, we obtained proteomic profiles of the vancomycin-resistant Enterococcus faecium SU18 strain treated with and without vancomycin. Fourteen proteins were differentially expressed in SU18, seven of which were up-regulated and seven down-regulated. Proteins involved in the vancomycin resistance mechanism, such as the VanA protein, VanA ligase, VanR and D-Ala-D-Ala dipeptidase, were up-regulated in the presence of vancomycin, while metabolism-related proteins, such as triosephosphate isomerase, guanine monophosphate synthase and glyceraldehyde-3-phosphate dehydrogenase were down-regulated. Overall the compensatory response of SU18 to antibiotics is to alter expression of proteins related to antibiotic resistance, cell wall formation and energy metabolism. Some of the differentially expressed proteins might enhance antimicrobial activity and are now being investigated as potential therapeutic drug targets in other pathogenic bacteria.
This study highlights the power of proteomics in the study of differential protein expression in a multiresistant Enterococcus faecium strain when subjected to vancomycin stress.
肠球菌并非高致病性细菌，但该微生物群临床分离株中万古霉素耐药性的发生率正在稳步上升，对公共卫生构成威胁。耐万古霉素肠球菌是目前最难对付的一些医院相关病原体，迫切需要新的治疗方法。为了解细菌对糖肽类抗生素耐药的分子机制，我们获得了经万古霉素处理和未处理的耐万古霉素屎肠球菌SU18菌株的蛋白质组图谱。SU18中有14种蛋白质差异表达，其中7种上调，7种下调。参与万古霉素耐药机制的蛋白质，如VanA蛋白、VanA连接酶、VanR和D-丙氨酰-D-丙氨酸二肽酶，在万古霉素存在时上调，而与代谢相关的蛋白质，如磷酸丙糖异构酶、鸟苷单磷酸合酶和甘油醛-3-磷酸脱氢酶则下调。总体而言，SU18对抗生素的补偿反应是改变与抗生素耐药性、细胞壁形成和能量代谢相关的蛋白质表达。一些差异表达的蛋白质可能会增强抗菌活性，目前正在作为其他病原菌潜在的治疗药物靶点进行研究。
本研究突出了蛋白质组学在研究多重耐药屎肠球菌菌株在万古霉素应激下差异蛋白质表达方面的作用。
