Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USA.
Veterinary Diagnostic Laboratory, Department of Veterinary Population Medicine, University of Minnesota, Saint Paul, MN 55108, USA.
Int J Mol Sci. 2021 Aug 19;22(16):8938. doi: 10.3390/ijms22168938.
The development and spread of antibiotics and biocides resistance is a significant global challenge. To find a solution for this emerging problem, the discovery of novel bacterial cellular targets and the critical pathways associated with antimicrobial resistance is needed. In the present study, we investigated the role of the two most critical envelope stress response regulators, RpoE and CpxR, on the physiology and susceptibility of growing serovar cells using the polycationic antimicrobial agent, chlorhexidine (CHX). It was shown that deletion of the gene significantly increased the susceptibility of this organism, whereas deletion of the gene had no effect on the pathogen's susceptibility to this antiseptic. It has been shown that a lack of the CpxR regulator induces multifaceted stress responses not only in the envelope but also in the cytosol, further affecting the key biomolecules, including DNA, RNA, and proteins. We showed that alterations in cellular trafficking and most of the stress responses are associated with a dysfunctional CpxR regulator during exponential growth phase, indicating that these physiological changes are intrinsically associated with the lack of the CpxR regulator. In contrast, induction of type II toxin-antitoxin systems and decrease of abundances of enzymes and proteins associated with the recycling of muropeptides and resistance to polymixin and cationic antimicrobial peptides were specific responses of the ∆ mutant to the CHX treatment. Overall, our study provides insight into the effects of CpxR on the physiology of . Enteritidis cells during the exponential growth phase and CHX treatment, which may point to potential cellular targets for the development of an effective antimicrobial agent.
抗生素和消毒剂耐药性的发展和传播是一个重大的全球挑战。为了解决这个新出现的问题，需要发现新的细菌细胞靶标和与抗菌药物耐药性相关的关键途径。在本研究中，我们使用多阳离子抗菌剂洗必泰（CHX）研究了两个最关键的包膜应激反应调节剂 RpoE 和 CpxR 在 血清型细胞生长和易感性中的作用。结果表明，该基因的缺失显著增加了该生物的易感性，而该基因的缺失对病原体对这种防腐剂的敏感性没有影响。已经表明，CpxR 调节剂的缺乏不仅会在包膜中，而且会在细胞质中诱导多方面的应激反应，进一步影响关键生物分子，包括 DNA、RNA 和蛋白质。我们表明，在指数生长期，细胞运输的改变和大多数应激反应与功能失调的 CpxR 调节剂有关，表明这些生理变化与缺乏 CpxR 调节剂密切相关。相比之下，II 型毒素-抗毒素系统的诱导和与肽聚糖回收和多粘菌素及阳离子抗菌肽抗性相关的酶和蛋白质丰度的降低是 ∆突变体对 CHX 处理的特异性反应。总的来说，我们的研究深入了解了 CpxR 在指数生长期和 CHX 处理时对 肠炎沙门氏菌细胞生理学的影响，这可能为开发有效的抗菌剂指明了潜在的细胞靶标。
