High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae.
High Osmotic Stress Increases OmpK36 Expression through the Regulation of KbvR to Decrease the Antimicrobial Resistance of Klebsiella pneumoniae.
复制标题
高渗透压通过调节 KbvR 增加 OmpK36 表达，降低肺炎克雷伯菌的耐药性
DOI：
10.1128/spectrum.00507-22
复制
发表时间：
2022-06-29
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肺炎克雷伯氏菌是一种以其高频率的抗菌素耐药性而闻名的病原体。在其生命过程中对各种环境压力的反应可以影响对抗生素的抗性。在这里，我们展示的作用和机制KbvR调节器在响应环境渗透胁迫和渗透胁迫对抗生素耐药性的影响。kbvR突变株表现出对高渗透胁迫和某些抗生素（包括β-内酰胺类）的耐受性增加。在野生型（WT）中，KbvR和外膜孔蛋白OmpK 36的表达水平响应于高渗透胁迫而上调，并且KbvR的缺失降低了OmpK 36的表达水平。kbvR突变株的膜通透性降低，这是通过上调OmpK 36的表达部分恢复。DNA亲和纯化测序（DAP-seq）和微量热泳（MST）分析揭示了KbvR与ompK 36基因的启动子的结合，表明KbvR直接且正调控OmpK 36的表达。高渗胁迫使WT株对β-内酰胺类药物的敏感性增加，ompK 36的表达增加。而在高渗胁迫下，突变株ompK 36表达量的增加和对β-内酰胺类药物的敏感性均低于野生型。总之，我们的研究证实了环境中的高渗透胁迫影响了K. KbvR与OmpR共同调控OmpK 36的表达，可能参与了抵抗高渗胁迫，从而改变细菌的耐药性。重要性肺炎克雷伯菌被认为是一个全球性的威胁，因为多药耐药菌株的流行率上升，他们的最佳适应临床环境和人类宿主。细菌对环境渗透胁迫的感受和适应能力可以改变其外膜孔蛋白的表达、膜通透性和对抗生素的抗性。本研究报道KbvR是一种新发现的调节因子，在高渗胁迫下可上调其表达，并直接调节OmpK 36的表达，从而改变K.β-内酰胺类抗生素。结果表明，对高渗胁迫的适应改变了K。肺炎抗生素。该机制可用于使细菌对抗生素敏感，并突出利用共同限制来管理适应各种环境挑战的新的潜在策略。
Klebsiella pneumoniae is a pathogen known for its high frequency of antimicrobial resistance. Responses to various environmental stresses during its life can influence the resistance to antibiotics. Here, we demonstrate the role and mechanism of KbvR regulator in the response to environmental osmotic stress and in the effect of osmotic stress on antimicrobial resistance. The kbvR mutant strain exhibited increasing tolerance to high osmotic stress and certain antibiotics, including β-lactams. The expression levels of KbvR and outer membrane porin OmpK36 were upregulated in response to high osmotic stress in the wild type (WT), and the deletion of kbvR decreased the expression level of ompK36. The membrane permeability of the kbvR mutant strain was decreased, which was partly restored through the upregulated expression of OmpK36. The DNA affinity purification sequencing (DAP-seq) and microscale thermophoresis (MST) assay disclosed the binding of KbvR to the promoter of the ompK36 gene, indicating that KbvR directly and positively regulated the expression of OmpK36. The high osmotic stress increased the susceptibility to β-lactams and the expression of ompK36 in the WT strain. However, the increased ompK36 expression and the susceptibility to β-lactams in the kbvR mutant strain under high osmotic stress were lower than those of WT. In conclusion, our study has identified that high osmotic stress in the environment influenced the resistance of K. pneumoniae to antibiotics and that the regulation of KbvR with OmpR on the expression of OmpK36 was involved in countering high osmotic stress to change the antimicrobial resistance. IMPORTANCE Klebsiella pneumoniae is considered a global threat because of the rising prevalence of multidrug-resistant strains and their optimal adaptation to clinical environments and the human host. The sensing and adaption abilities of bacteria to the environmental osmotic stress can change the expression of their outer membrane porins, membrane permeability, and resistance to antibiotics. This study reports that KbvR is a newly found regulator that can be upregulated under high osmotic stress and directly regulate the expression of OmpK36 to change the resistance of K. pneumoniae to β-lactam antibiotics. The results demonstrate how adaptation to high osmotic stress changes the sensitivity of K. pneumoniae to antibiotics. The mechanism can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints in governing adaptation to diverse environmental challenges.
登录
查看更多内容
影响因子：
6.7
作者：
Jung HJ;Sorbara MT;Pamer EG
通讯作者：
Pamer EG
影响因子：
1.1
作者：
Arnold RS;Thom KA;Sharma S;Phillips M;Kristie Johnson J;Morgan DJ
通讯作者：
Morgan DJ
DOI：
10.1016/j.bbapap.2008.11.005
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Delcour AH
通讯作者：
Delcour AH
DOI：
10.1016/j.eimc.2008.09.006
发表时间：
2009-11-01
影响因子：
2.5
作者：
Angel Diaz, Miguel;Ramon Hernandez, Jose;Pascual, Alvaro
通讯作者：
Pascual, Alvaro
影响因子：
5.2
作者：
de Cristobal, Ricardo E.;Vincent, Paula A.;Salomon, Raul A.
通讯作者：
Salomon, Raul A.