Objective: To investigate the prevalence of Salmonella Typhi and Paratyphi resistance to quinolones and characterize the underlying mechanism in Jiangsu Province of China. Methods: Antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion system. Quinolone resistance-determining region (QRDR), plasmid-mediated quinolone resistance (PMQR) determinant genes were detected by PCR and sequencing. Results: Out of 239 Salmonella isolates, 164 were S. Typhi and 75 were S. Paratyphi. 128 (53.6%) Salmonella isolates were resistant to nalidixic acid; 11 (4.6%) isolates to ciprofloxacin and 66 (27.6%) isolates were intermediate to ciprofloxacin. QRDR were present in 69 S. Typhi isolates, among which mutation at codon 83 (n = 45) and 133 (n = 61) predominated. In S. Paratyphi, the most common mutations were detected in gyrA at codon 83(n = 24) and parC: T57S (n = 8). Seven mutations were first reported in Salmonella isolates including gyrB: S426G, parC: D79G and parE: [S498T, E543K, V560G, I444S, Y434S]. PMQR genes including qnrD1, qnrA1, qnrB4, aac (6′)-Ib-cr4 and qnrS1 were detected in 1, 2, 3, 7 and 9 isolates, relatively. Conclusions: High resistance to quinolones in Salmonella remains a serious problem in Jiangsu, China. The presence of the novel mutations increases the complexity of quinolone-resistant genotypes and poses a threat to public health. Subject terms: Salmonella Typhi, Salmonella Paratyphi, antimicrobial resistance, QRDR, PMQR.

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Clostridioides difficile sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for C. difficile ST37 isolates. The 325 ST37 genomes from six continents, including North America (n=66), South America (n=4), Oceania (n=7), Africa (n=9), Europe (n=138) and Asia (n=101), were clustered into six major lineages, with region-dependent distributions, harbouring an array of antibioticresistance genes. The ST37 strains from China were divided into four distinct sublineages, showing five importation times and international sources. Isolates associated with severe infections exhibited significantly higher toxin productions, tcdB mRNA levels, and sporulation capacities (P < 0.001). Kyoto Encyclopedia of Genes and Genomes analysis showed 10 metabolic pathways were significantly enriched in the mutations among isolates associated with severe CDI (P < 0.05). Gene mutations in glycometabolism, amino acid metabolism and biosynthesis virtually causing instability in protein activity were correlated positively to the transcription of tcdR and negatively to the expression of toxin repressor genes, ccpA and codY. In summary, our study firstly presented genomic insights into genetic characteristics and virulence association of C. difficile ST37 in China. Gene mutations in certain important metabolic pathways are associated with severe symptoms and correlated with higher virulence in C. difficile ST37 isolates.