Yoon Eun-Jeong, Mo Jun Won, Kim Jee-Woong, Jeong Min Chul, Yoo Jung Sik
Division of Antimicrobial Resistance Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea.
Division of Research Support, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si 28159, Republic of Korea.
Microorganisms. 2024 Aug 11;12(8):1644. doi: 10.3390/microorganisms12081644.
is often highly resistant to multiple antimicrobials, posing a risk of treatment failure, and colistin is a "last resort" for treatment of the bacterial infection. However, colistin resistance is easily developed when the bacteria are exposed to the drug, and a comprehensive analysis of colistin-mediated changes in colistin-susceptible and -resistant is needed. In this study, using an isogenic pair of colistin-susceptible and -resistant isolates, alterations in morphologic and transcriptomic characteristics associated with colistin resistance were revealed. Whole-genome sequencing showed that the resistant isolate harbored a PmrB mutation conferring colistin resistance, and all other single-nucleotide alterations were located in intergenic regions. Using scanning electron microscopy, it was determined that the colistin-resistant mutant had a shorter cell length than the parental isolate, and filamented cells were found when both isolates were exposed to the inhibitory concentration of colistin. When the isolates were treated with inhibitory concentrations of colistin, more than 80% of the genes were upregulated, including genes associated with antioxidative stress response pathways. The results elucidate the morphological difference between the colistin-susceptible and -resistant isolates and different colistin-mediated responses in isolates depending on their susceptibility to this drug.
通常对多种抗菌药物具有高度抗性，存在治疗失败的风险，而黏菌素是治疗该细菌感染的“最后手段”。然而，当细菌接触该药物时，很容易产生黏菌素抗性，因此需要对黏菌素敏感和耐药菌株中黏菌素介导的变化进行全面分析。在本研究中，使用一对同源的黏菌素敏感和耐药菌株，揭示了与黏菌素抗性相关的形态和转录组特征的变化。全基因组测序表明，耐药菌株存在一个赋予黏菌素抗性的PmrB突变，所有其他单核苷酸改变均位于基因间区域。使用扫描电子显微镜确定，黏菌素耐药突变体的细胞长度比亲本菌株短，并且当两种菌株都暴露于黏菌素抑制浓度时发现了丝状细胞。当菌株用黏菌素抑制浓度处理时，超过80%的基因上调，包括与抗氧化应激反应途径相关的基因。结果阐明了黏菌素敏感和耐药菌株之间的形态差异，以及不同菌株对黏菌素的介导反应取决于它们对该药物的敏感性。
