Nabu Sunanta, Lawung Ratana, Isarankura-Na-Ayudhya Patcharee, Roytrakul Sittiruk, Dolprasit Supamas, Sengyee Sineenart, Isarankura-Na-Ayudhya Chartchalerm, Prachayasittikul Virapong
Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
Center of Medical Laboratory Services, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
EXCLI J. 2017 Nov 8;16:1207-1229. doi: 10.17179/excli2017-832. eCollection 2017.
strains displaying reduced susceptibility and resistance to extended-spectrum cephalosporins (ESCs) are major public health concerns. Although resistance mechanisms of ESCs have extensively been studied, the proteome-wide investigation on the biological response to the antibiotic stress is still limited. Herein, a proteomics approach based on two-dimensional gel electrophoresis and MALDI-TOF/TOF-MS analysis was applied to investigate the global protein expression under ESC stresses of ESC-susceptible and ESC-reduced susceptible strains. Upon exposure to ceftriaxone, 14 and 21 proteins of ESC-susceptible and ESC-reduced susceptible strains, respectively, were shown to be differentially expressed. In the meanwhile, differential expressions of 13 and 17 proteins were detected under cefixime stress for ESC-susceptible and ESC-reduced susceptible strains, respectively. ESC antibiotics have been proven to trigger the expression of several proteins implicated in a variety of biological functions including transport system, energy metabolism, stress response and pathogenic virulence factors. Interestingly, macrophage infectivity potentiators (Ng-MIP) showed increased expression for ESC-reduced susceptible strain under ESC stress. The altered expression of Ng-MIP was found to be a unique response to ESC stresses. Our finding proposes a broad view on proteomic changes in in response to ESC antibiotics that provides further insights into the gonococcal antimicrobial resistance and physiological adaptation mechanism.
对超广谱头孢菌素（ESCs）敏感性降低和耐药的菌株是主要的公共卫生问题。尽管对ESCs的耐药机制已进行了广泛研究，但对抗生素应激的生物学反应进行全蛋白质组研究仍然有限。在此，基于二维凝胶电泳和基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF-MS）分析的蛋白质组学方法被用于研究ESCs敏感菌株和ESCs敏感性降低菌株在ESCs应激下的整体蛋白质表达。暴露于头孢曲松后，ESCs敏感菌株和ESCs敏感性降低菌株分别有14种和21种蛋白质显示出差异表达。同时，在头孢克肟应激下，ESCs敏感菌株和ESCs敏感性降低菌株分别检测到13种和17种蛋白质的差异表达。已证实ESCs抗生素会触发多种蛋白质的表达，这些蛋白质涉及多种生物学功能，包括转运系统、能量代谢、应激反应和致病毒力因子。有趣的是，巨噬细胞感染增强因子（Ng-MIP）在ESCs应激下，ESCs敏感性降低菌株中的表达增加。发现Ng-MIP表达的改变是对ESCs应激的独特反应。我们的发现为响应ESCs抗生素的蛋白质组变化提供了一个广阔的视角，这为淋球菌的抗菌耐药性和生理适应机制提供了进一步的见解。
