University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Laboratory of Immune System Biology (LISB), National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20814, USA.
Pathog Dis. 2019 Mar 1;77(2). doi: 10.1093/femspd/ftz005.
Melioidosis associated with opportunistic pathogen Burkholderia pseudomallei imparts a huge medical burden in Southeast Asia and Australia. At present there is no available human vaccine that protects against B. pseudomallei infection and antibiotic treatments are limited particularly for drug-resistant strains and bacteria in biofilm forms. Biofilm forming bacteria exhibit phenotypic features drastically different to their planktonic states, often exhibiting a diminished response to antimicrobial therapies. Our earlier work on global profiling of bacterial biofilms using transcriptomics and proteomics revealed transcript-decoupled protein abundance in bacterial biofilms. Here we employed reverse phase liquid chromatography tandem mass spectrometry (LC-MS/MS) to deduce temporal proteomic differences in planktonic and biofilm forms of Burkholderia thailandensis, which is weakly surrogate model of pathogenic B. pseudomallei as sharing a key element in genomic similarity. The proteomic analysis of B. thailandensis in biofilm versus planktonic states revealed that proteome changes support biofilm survival through decreased abundance of metabolic proteins while increased abundance of stress-related proteins. Interestingly, the protein abundance including for the transcription protein TEX, outer periplasmic TolB protein, and the exopolyphosphatase reveal adaption in bacterial biofilms that facilitate antibiotic tolerance through a non-specific mechanism. The present proteomics study of B. thailandensis biofilms provides a global snapshot of protein abundance differences and antimicrobial sensitivities in planktonic and sessile bacteria.
类鼻疽病是由机会性病原体伯克霍尔德菌引起的，给东南亚和澳大利亚带来了巨大的医疗负担。目前，尚无可用的人类疫苗能预防伯克霍尔德菌感染，抗生素治疗也受到限制，特别是针对耐药菌株和生物膜形式的细菌。生物膜形成的细菌表现出与浮游状态明显不同的表型特征，通常对抗菌治疗的反应减弱。我们之前使用转录组学和蛋白质组学对细菌生物膜的全球分析表明，细菌生物膜中存在转录偶联蛋白丰度降低的现象。在这里，我们使用反相液相色谱串联质谱（LC-MS/MS）来推断浮游和生物膜形式的伯克霍尔德菌泰国亚种的时间蛋白质组差异，该菌是致病性伯克霍尔德菌的弱替代模型，因为它们在基因组相似性方面有一个关键元素。生物膜与浮游状态的 B. thailandensis 的蛋白质组分析表明，蛋白质组的变化通过减少代谢蛋白的丰度来支持生物膜的存活，同时增加应激相关蛋白的丰度。有趣的是，包括转录蛋白 TEX、外周质 TolB 蛋白和外多磷酸盐酶在内的蛋白质丰度的变化表明，细菌生物膜中的适应能力通过非特异性机制促进了抗生素耐药性。本研究对 B. thailandensis 生物膜的蛋白质组学研究提供了浮游和定殖细菌在蛋白质丰度差异和抗菌敏感性方面的全局快照。
