The PhoRP two-component system (TCS), one of the most important signaling pathways in Bacillus subtilis, regulates cell physiological reactions mainly under phosphate starvation conditions. The mechanism by which PhoRP TCS regulates resistance towards antibiotics in B. subtilis strain NCD-2 was investigated in this study. Using phenotype microarray (PM) technology, the susceptibility of B. subtilis to 240 antimicrobial compounds was compared among the wild-type strain NCD-2, the phoR-null mutant (MR), and the phoP-null mutant (MP). Compared with the wild type, the MR mutant was more resistant to 13 antibiotics with different functions, and the MP mutant was more resistant to 14 antibiotics, of which 8 were 30S/50S ribosome-targeted. To investigate the molecular mechanisms involved in changing the level of antibiotic resistance, transcriptional analysis was performed to compare the differentially expressed genes among the wild-type strain and the MR and MP mutants. Compared with the wild-type strain, 294 genes were differentially expressed in the MR mutant, including 97 up-regulated genes and 197 down-regulated genes. Most of the differently expressed genes were associated with carbohydrate mechanism, amino acid mechanism, ABC-transporters and phosphotransferase systems. A total of 212 genes were differentially expressed in the MP mutant, including 10 up-regulated genes and 202 down-regulated genes, and most were associated with ribosome synthesis, amino acid metabolism, carbohydrate metabolism and ABC-transporters. The khtSTU operon (encoding the K⁺ efflux pump) that was up-regulated in the MP mutant was deleted by in-frame deletion in the MP mutant. The phoP and khtSTU operon double mutant MPK showed decreased antibiotic resistance to doxycycline, chlortetracycline, spiramycin, puromycin, and paromomycin when compared with the MP mutant. Thus, the results indicated that the khtSTU operon was responsible for the PhoP-mediated multiple antibiotic resistance.

PhoRP两组分系统（TCS）是枯草芽孢杆菌中最重要的信号传导途径之一，主要在磷酸盐饥饿的条件下调节细胞的生理反应。在这项研究中，研究了PhoRP TCS调节枯草芽孢杆菌NCD-2菌株对抗生素的抗性的机制。使用表型微阵列（PM）技术，比较了野生型菌株NCD-2，phoR - null突变体（MR）和phoP中枯草芽孢杆菌对240种抗菌化合物的敏感性。-空突变体（MP）。与野生型相比，MR突变体对13种功能不同的抗生素更具抗性，而MP突变体对14种抗生素具有更强的抗性，其中8种是针对30S / 50S核糖体的。为了研究涉及改变抗生素抗性水平的分子机制，进行了转录分析，以比较野生型菌株与MR和MP突变体之间差异表达的基因。与野生型菌株相比，在MR突变体中差异表达了294个基因，包括97个上调基因和197个下调基因。大多数差异表达的基因与碳水化合物机制，氨基酸机制，ABC转运蛋白和磷酸转移酶系统有关。共有212个基因在MP突变体中差异表达，其中包括10个上调基因和202个下调基因，并且大多数与核糖体合成，氨基酸代谢，碳水化合物代谢和ABC转运蛋白有关。的通过在MP突变体中进行框内删除来删除在MP突变体中上调的khtSTU操纵子（编码K ⁺外排泵）。所述phoP基因和khtSTU操纵子双重突变体显示出MPK当与MP相比突变体抗生素抗性降低到多西环素，金霉素，螺旋霉素，嘌呤霉素，巴龙霉素和。因此，结果表明，khtSTU操纵子负责PhoP介导的多种抗生素耐药性。