Details

Autor(en) / Beteiligte

• Zhong, Tairan
• Wu, Haiming
• Hu, Jiehua
• Liu, Yun
• Zheng, Yundan
• Li, Nan
• Sun, Zhenghua
• Yin, Xing-Feng
• He, Qing-Yu
• Sun, Xuesong

Titel

Two synonymous single-nucleotide polymorphisms promoting fluoroquinolone resistance of Escherichia coli in the environment

Ist Teil von

• Journal of hazardous materials, 2024-05, Vol.469, p.133849, Article 133849

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Single-nucleotide polymorphism (SNP) is one of the core mechanisms that respond to antibiotic resistance of Escherichia coli (E. coli), which is a major issue in environmental pollution. A specific type of SNPs, synonymous SNPs, have been generally considered as the “silent” SNPs since they do not change the encoded amino acid. However, the impact of synonymous SNPs on mRNA splicing, nucleo-cytoplasmic export, stability, and translation was gradually discovered in the last decades. Figuring out the mechanism of synonymous SNPs in regulating antibiotic resistance is critical to improve antimicrobial therapy strategies in clinics and biological treatment strategies of antibiotic-resistant E. coli-polluted materials. With our newly designed antibiotic resistant SNPs prediction algorithm, Multilocus Sequence Type based Identification for Phenotype-single nucleotide polymorphism Analysis (MIPHA), and in vivo validation, we identified 2 important synonymous SNPs 522 G>A and 972 C>T, located at hisD gene, which was previously predicted as a fluoroquinolone resistance-related gene without a detailed mechanism in the E. coli samples with environmental backgrounds. We first discovered that hisD causes gyrA mutation via the upregulation of sbmC and its downstream gene umuD. Moreover, those 2 synonymous SNPs of hisD cause its own translational slowdown and further reduce the expression levels of sbmC and its downstream gene umuD, making the fluoroquinolone resistance determining region of gyrA remains unmutated, ultimately causing the bacteria to lose their ability to resist drugs. This study provided valuable insight into the role of synonymous SNPs in mediating antibiotic resistance of bacteria and a new perspective for the treatment of environmental pollution caused by drug-resistant bacteria. [Display omitted] •4598 samples of E. coli WGS and phenotype data, including 3533 samples with environmental background were analyzed.•Two synonymous Single-Nucleotide Polymorphisms that disable hisD functionality were screened by a new developed algorithm.•hisD promotes E. coli fluoroquinolone resistantce by increasing the expression of sbmC and umuD.•The synonymous SNPs cause translational slowdown of HisD and disturb its antibiotic resistant function.