Li Mengchen, Liu Qiaoli, Teng Yanli, Ou Liuyang, Xi Yuanlin, Chen Shuaiyin, Duan Guangcai
Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical College, Xinxiang, Henan, People's Republic of China.
Infect Drug Resist. 2019 Sep 11;12:2853-2863. doi: 10.2147/IDR.S221212. eCollection 2019.
Multi-drug-resistant poses a great threat to human health, especially resistant to ampicillin (AMP), but the mechanism of drug resistance is not very clear.
To understand the mechanism of resistance of to beta-lactam antibiotics by inducing drug resistance of sensitive bacteria in laboratory.
Clinical sensitive strain was induced into resistance strain by 1/2 minimum inhibitive concentration (MIC) induced trails of AMP. The drug resistance spectrum was measured by modified K-B susceptibility test. Whole-genome sequencing analysis was used to analyze primary sensitive strain, and resequencing was used to analyze induced strains. Protein tertiary structure encoded by the gene containing single nucleotide polymorphism (SNP) was analyzed by bioinformatics.
After 315 hrs induced, the MIC value of reached to 256 µg/mL, 64 times higher than that of the sensitive bacteria. During the induction process, the bacterial resistance process is divided into two stages. The rate of drug resistance occurs rapidly before reaching the critical concentration of 32 µg/mL, and then the resistance rate slows down. Sequencing of the genome of resistant strain showed that drug-resistant strain with the MIC values of 32 and 256 µg/mL contained four and eight non-synonymous SNPs, respectively. These non-synonymous SNPs were distributed in the genes of , and
These studies will improve our understanding of the molecular mechanism of AMP resistance of , and may provide the basis for prevention and control of multi-drug-resistant bacteria and generation of new antibiotics to treat infection.
多重耐药性对人类健康构成巨大威胁，尤其是对氨苄西林（AMP）耐药，但耐药机制尚不完全清楚。
通过在实验室诱导敏感菌耐药，了解其对β-内酰胺类抗生素的耐药机制。
采用1/2最低抑菌浓度（MIC）的AMP诱导试验，将临床敏感菌株诱导为耐药菌株。采用改良K-B药敏试验测定耐药谱。对原始敏感菌株进行全基因组测序分析，对诱导菌株进行重测序。利用生物信息学分析含有单核苷酸多态性（SNP）的基因编码的蛋白质三级结构。
诱导315小时后，该菌的MIC值达到256μg/mL，比敏感菌高64倍。在诱导过程中，细菌耐药过程分为两个阶段。在达到32μg/mL的临界浓度之前，耐药率迅速上升，之后耐药率减缓。耐药菌株基因组测序显示，MIC值为32和256μg/mL的耐药菌株分别含有4个和8个非同义SNP。这些非同义SNP分布在……基因中。
这些研究将提高我们对该菌对AMP耐药分子机制的认识，并可能为多重耐药菌的防控及治疗该菌感染的新型抗生素研发提供依据。
