ACS Nano. 2018 Mar 27;12(3):2728-2740. doi: 10.1021/acsnano.7b08977. Epub 2018 Feb 26.
Carbonaceous and boron nitride (BN) nanomaterials have similar applications and hydrophobic properties suggesting common release pathways and exposure to bacteria. While high nanomaterial concentrations can be bactericidal or growth-inhibitory, little is known regarding bacterial transcriptional responses to non-growth-inhibitory nanomaterial concentrations. Here, using one strain of Pseudomonas aeruginosa-a clinically and environmentally important bacterial taxon-we analyzed the comparative transcriptomic response to carbonaceous or BN nanomaterials. We show that, at non-growth-inhibitory, equal mass concentrations (10 mg/L), multiwall carbon nanotubes (MWCNTs) induced differential regulation of 111 genes in P. aeruginosa, while graphene, BN, and carbon black caused differential regulation of 44, 26, and 25 genes, respectively. MWCNTs caused the upregulation of genes encoding general stress response (9 genes), sulfur metabolism (15), and transport of small molecules (7) and downregulation of genes encoding flagellar basal-body rod proteins and other virulence-related factors (6), nitrogen metabolism (7), and membrane proteins (12), including a two-component regulatory system CzcS/R. Because two-component systems are associated with antibiotic resistance, the antibiotic susceptibility of P. aeruginosa was tested following MWCNT exposure. In MWCNT-treated cultures, the minimal inhibitory concentrations (MICs) of meropenem and imipenem decreased from 0.06 to 0.03 μg/mL and from 0.25 to 0.125 μg/mL, respectively. Taken together, whole genome analysis indicated that, in the absence of growth inhibition, nanomaterials can alter bacterial physiology and metabolism. For MWCNTs, such alterations may include downregulation of antibiotic resistance pathways, suggesting that pre-exposure to MWCNTs could potentially render bacteria more susceptible to carbapenems which are often the last resort for the globally concerning, highly antibiotic resistant P. aeruginosa.
碳质和氮化硼(BN)纳米材料具有相似的应用和疏水性,这表明它们可能具有共同的释放途径和暴露于细菌的风险。虽然高浓度的纳米材料可能具有杀菌或生长抑制作用,但对于非生长抑制浓度的纳米材料对细菌转录反应的影响知之甚少。在这里,我们使用一种铜绿假单胞菌(一种临床和环境上重要的细菌分类群)来分析其对碳质或 BN 纳米材料的比较转录组响应。我们表明,在非生长抑制浓度(10mg/L)下,多壁碳纳米管(MWCNTs)诱导铜绿假单胞菌中 111 个基因的差异调节,而石墨烯、BN 和炭黑分别导致 44、26 和 25 个基因的差异调节。MWCNTs 导致编码一般应激反应(9 个基因)、硫代谢(15 个基因)和小分子转运(7 个基因)的基因上调,而鞭毛基部杆状蛋白和其他与毒力相关的因子(6 个基因)、氮代谢(7 个基因)和膜蛋白(12 个基因)的基因下调,包括一个双组分调控系统 CzcS/R。由于双组分系统与抗生素耐药性相关,因此在暴露于 MWCNT 后测试了铜绿假单胞菌的抗生素敏感性。在 MWCNT 处理的培养物中,美罗培南和亚胺培南的最小抑菌浓度(MIC)分别从 0.06 降至 0.03μg/mL 和从 0.25 降至 0.125μg/mL。总之,全基因组分析表明,在没有生长抑制的情况下,纳米材料可以改变细菌的生理和代谢。对于 MWCNTs,这种改变可能包括下调抗生素耐药途径,这表明预先暴露于 MWCNTs 可能使细菌对碳青霉烯类药物更敏感,而碳青霉烯类药物通常是对全球关注的、高度抗生素耐药的铜绿假单胞菌的最后手段。