The resistance mechanism of induced by ampicillin in laboratory.

BACKGROUND

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.

PURPOSE

To understand the mechanism of resistance of to beta-lactam antibiotics by inducing drug resistance of sensitive bacteria in laboratory.

METHODS

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.

RESULTS

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

CONCLUSION

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.