Sharma Divakar, Garg Anjali, Kumar Manish, Rashid Faraz, Khan Asad U
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
Department of Biophysics, University of Delhi, New Delhi, India.
Front Microbiol. 2019 Dec 17;10:2865. doi: 10.3389/fmicb.2019.02865. eCollection 2019.
The emergence and spread of carbapenem-resistant infections have worsened the current situation worldwide, in which totally drug-resistant strains (bad bugs) are becoming increasingly prominent. Bacterial biofilms enable bacteria to tolerate higher doses of antibiotics and other stresses, which may lead to the drug resistance. In the present study, we performed proteomics on the carbapenem-resistant NDM-4-producing e clinical isolate under meropenem stress. Liquid chromatography coupled with mass spectrometry (LC-MS/MS) analysis revealed that 69 proteins were down-regulated (≤0.42-fold change) under meropenem exposure. Within the identified down-regulated proteome (69 proteins), we found a group of 13 proteins involved in flagellar, fimbriae, and pili formation and their related functions. Further, systems biology approaches were employed to reveal their networking pathways. We suggest that these down-regulated proteins and their interactive partners cumulatively contribute to the emergence of a biofilm-like state and the survival of bacteria under drug pressure, which could reveal novel mechanisms or pathways involved in drug resistance. These down-regulated proteins and their pathways might be used as targets for the development of novel therapeutics against antimicrobial-resistant (AMR) infections.
耐碳青霉烯感染的出现和传播使全球目前的情况恶化，在这种情况下，完全耐药菌株（超级细菌）正变得日益突出。细菌生物膜使细菌能够耐受更高剂量的抗生素和其他压力，这可能导致耐药性。在本研究中，我们对处于美罗培南压力下的产耐碳青霉烯NDM-4的临床分离株进行了蛋白质组学研究。液相色谱-质谱联用（LC-MS/MS）分析显示，在美罗培南暴露下，有69种蛋白质表达下调（变化倍数≤0.42倍）。在鉴定出的下调蛋白质组（69种蛋白质）中，我们发现一组13种蛋白质参与鞭毛、菌毛和菌毛的形成及其相关功能。此外，采用系统生物学方法来揭示它们的网络通路。我们认为，这些下调的蛋白质及其相互作用伙伴共同促成了生物膜样状态的出现以及细菌在药物压力下的存活，这可能揭示了耐药性涉及的新机制或新通路。这些下调的蛋白质及其通路可能被用作开发抗耐药性（AMR）感染新疗法的靶点。
