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Chronic Exposure to Low Concentration of Graphene Oxide Increases Bacterial Pathogenicity via the Envelope Stress Response.
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2020-09-10 , DOI: 10.1021/acs.est.0c04538 Qiurong Zhang 1, 2 , Chengdong Zhang 1
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2020-09-10 , DOI: 10.1021/acs.est.0c04538 Qiurong Zhang 1, 2 , Chengdong Zhang 1
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Graphene oxide (GO), which has diverse antimicrobial mechanisms, is a promising material to address antibiotic resistance. Considering the emergence of antibiotic tolerance/resistance due to prolonged exposure to sublethal antibiotics, it is imperative to assess the microbiological effects and related adaptive mechanisms under chronic exposure to sublethal levels of GO, which have rarely been explored. After repetitive exposure to 5 mg/L GO for 200 subcultures (400 days), evolved Escherichia coli (E. coli) cells (EGO) differed significantly from their ancestor cells according to transcriptomic and metabolomic analyses. Contact with GO surfaces transformed E. coli by activating the Cpx envelope stress response (ESR), resulting in more than twofold greater extracellular protease release and biofilm formation. The ESR also modulated the envelope structure and function via increases in membrane fluidity, permeation, and lipopolysaccharide content to fulfill growth requirements and combat envelope stress. As a consequence of metabolic adjustment, EGO cells showed advantages of surviving in an acidic and oxidative environment, which resembles the cytosol of host cells. With these adaptive features, EGO cells exhibited higher pathogenicity than ancestor E. coli cells as evidenced by increased bacterial invasion and intracellular survival and a more severe inflammatory response in macrophage cells. To conclude, we seek to raise awareness of the possible occurrence of microbial adaptation to antimicrobial nanomaterials, which may be implicated in cross-adaptation to harsh environments and eventually the prevalence of virulence.
中文翻译：
长期暴露于低浓度的氧化石墨烯会通过包膜应力反应增加细菌的致病性。
氧化石墨烯（GO）具有多种抗菌机制，是解决抗生素耐药性的有前途的材料。考虑到由于长时间暴露于亚致死性抗生素引起的抗生素耐受性/耐药性的出现，必须评估长期暴露于GO致死性水平下的微生物效应和相关的适应机制，这一点很少被探讨。经过200次传代培养（400天）反复暴露于5 mg / L GO后，根据转录组和代谢组学分析，进化的大肠杆菌（E. coli）细胞（E GO）与祖先细胞有显着差异。与GO表面接触转化的大肠杆菌通过激活Cpx包膜应激反应（ESR），导致细胞外蛋白酶释放和生物膜形成增加两倍以上。ESR还通过增加膜的流动性，渗透性和脂多糖含量来调节包膜结构和功能，从而满足生长要求并抵抗包膜应力。作为代谢调节的结果，E GO细胞显示出在酸性和氧化性环境中存活的优势，这类似于宿主细胞的细胞质。具有这些适应性特征的E GO细胞具有比祖先大肠杆菌更高的致病性细菌侵袭和细胞内存活增加以及巨噬细胞中更严重的炎症反应所证明。总而言之，我们寻求提高人们对微生物对抗菌纳米材料适应性可能发生的认识，这可能与对恶劣环境的交叉适应以及最终的致病性有关。
更新日期：2020-10-06
中文翻译：
长期暴露于低浓度的氧化石墨烯会通过包膜应力反应增加细菌的致病性。
氧化石墨烯（GO）具有多种抗菌机制，是解决抗生素耐药性的有前途的材料。考虑到由于长时间暴露于亚致死性抗生素引起的抗生素耐受性/耐药性的出现，必须评估长期暴露于GO致死性水平下的微生物效应和相关的适应机制，这一点很少被探讨。经过200次传代培养（400天）反复暴露于5 mg / L GO后，根据转录组和代谢组学分析，进化的大肠杆菌（E. coli）细胞（E GO）与祖先细胞有显着差异。与GO表面接触转化的大肠杆菌通过激活Cpx包膜应激反应（ESR），导致细胞外蛋白酶释放和生物膜形成增加两倍以上。ESR还通过增加膜的流动性，渗透性和脂多糖含量来调节包膜结构和功能，从而满足生长要求并抵抗包膜应力。作为代谢调节的结果，E GO细胞显示出在酸性和氧化性环境中存活的优势，这类似于宿主细胞的细胞质。具有这些适应性特征的E GO细胞具有比祖先大肠杆菌更高的致病性细菌侵袭和细胞内存活增加以及巨噬细胞中更严重的炎症反应所证明。总而言之，我们寻求提高人们对微生物对抗菌纳米材料适应性可能发生的认识，这可能与对恶劣环境的交叉适应以及最终的致病性有关。
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