Kim Nayeong, Son Joo-Hee, Kim Kyeongmin, Kim Hyo-Jeong, Shin Minsang, Lee Je-Chul
Department of Microbiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Antibiotics (Basel). 2021 Nov 30;10(12):1472. doi: 10.3390/antibiotics10121472.
The stringent response regulators, (p)ppGpp and DksA, modulate various genes involved in physiological processes, virulence, and antimicrobial resistance in pathogenic bacteria. This study investigated the role of DksA in the antimicrobial susceptibility of . The ∆ mutant (KM0248D) of ATCC 17978 and its complemented strain (KM0248C) were used, in addition to the ∆ mutant strain (NY0298D) of clinical 1656-2 strain. The microdilution assay was used to determine the minimum inhibitory concentrations (MICs) of antimicrobial agents. Quantitative real-time PCR was performed to analyze the expression of genes associated with efflux pumps. The KM0248D strain exhibited an increase of MICs to quinolones and tetracyclines, whereas KM0248D and NY0298D strains exhibited a decrease of MICs to aminoglycosides. The expression of genes associated with efflux pumps, including , , , and/or , was upregulated in both ∆ mutant strains. The deletion of altered bacterial morphology in the clinical 1656-2 strain. In conclusion, DksA modulates the antimicrobial susceptibility of . The ∆ mutant strains of upregulate efflux pump gene expression, whereas (p)ppGpp-deficient mutants downregulate efflux pump gene expression. (p)ppGpp and DksA conduct opposite roles in the antimicrobial susceptibility of via efflux pump gene regulation.
严格反应调节因子(p)ppGpp和DksA可调节参与病原菌生理过程、毒力和抗菌抗性的各种基因。本研究调查了DksA在[具体细菌名称未给出]抗菌敏感性中的作用。除了临床1656 - 2菌株的Δ突变株(NY0298D)外,还使用了ATCC 17978的Δ突变株(KM0248D)及其互补菌株(KM0248C)。采用微量稀释法测定抗菌药物的最低抑菌浓度(MIC)。进行定量实时PCR分析与外排泵相关基因的表达。KM0248D菌株对喹诺酮类和四环素类药物的MIC增加,而KM0248D和NY0298D菌株对氨基糖苷类药物的MIC降低。在两个Δ突变株中,与外排泵相关的基因,包括[具体基因名称未给出]等的表达均上调。在临床1656 - 2菌株中,[具体基因名称未给出]的缺失改变了细菌形态。总之,DksA调节[具体细菌名称未给出]的抗菌敏感性。[具体细菌名称未给出]的Δ突变株上调外排泵基因表达,而(p)ppGpp缺陷型突变株下调外排泵基因表达。(p)ppGpp和DksA通过外排泵基因调控在[具体细菌名称未给出]的抗菌敏感性中发挥相反作用。