We confirmed the association of alanine, phenylalanine and tyrosine with future T2D risk and further identified palmitoylcarnitine as a novel metabolic marker of incident T2D in two prospective cohorts of Chinese adults. Our findings might provide new aetiological insight into the development of T2D.
The growing antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. Molecular typing is an ideal tool to reveal the association between specific genotype and resistance phenotype that provides effective data for tracking the transmission of resistant clones of N. gonorrhoeae. In our study, we aimed to describe the molecular epidemiology of AMR and the distribution of resistance-associated genotypes in Shenzhen during 2014–2018. In total, 909 isolates were collected from Shenzhen from 2014–2018. Two typing schemes, multilocus sequence typing (MLST) and N. gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR), were performed for all isolates. The distribution of resistance-associated genotypes was described using goeBURST analysis combined with data of logistic regression. Among 909 isolates, ST8123, ST7363, ST1901, ST7365, and ST7360 were most the common MLST sequence types (STs), and ST348, ST2473, ST497, and ST199 were the most prevalent NG-STAR STs. The logistic regression analysis showed that NG-STARST497, MLSTST7365, and MLSTST7360 were typically associated with decreased susceptibility to ceftriaxone. Furthermore, the internationally spreading ESC-resistant clone MLSTST1901 has been prevalent at least in 2014 in Shenzhen and showed a significant increase during 2014–2018. Additionally, MLSTST7363 owns the potential to become the next internationally spreading ceftriaxone-resistant ST. In conclusions, we performed a comprehensive epidemiological study to explore the correlation between AMR and specific STs, which provided important data for future studies of the molecular epidemiology of AMR in N. gonorrhoeae. Besides, these findings provide insight for adjusting surveillance strategies and therapy management in Shenzhen.
Background
Antimicrobial resistance (AMR) of Neisseria gonorrhoeae has spread worldwide. Rapid and comprehensive methods are needed to describe N. gonorrhoeae AMR profiles accurately. A method based on multiplex amplicon sequencing was developed to simultaneously sequence 13 genes related to AMR in N. gonorrhoeae directly from clinical samples.
Methods
Nine N. gonorrhoeae strains were used for the establishment and validation of the method. Eleven urethral swabs and their corresponding cultured isolates were matched as pairs to determine the accuracy of the method. Mock samples with different dilutions were prepared to determine the sensitivity of the method. Five nongonococcal Neisseria strains and 24 N. gonorrhoeae negative clinical samples were used to evaluate the cross-reactivity. Finally, the method was applied to 64 clinical samples to assess its performance.
Results
Using Sanger sequencing as a reference method, sequences recovered from amplicon sequencing had a base accuracy of over 99.5% and the AMR sites were correctly identified. The limit of detection (LOD) was lower than 31 copies/reaction. No significant cross-reactivity was observed. Furthermore, target genes were successfully recovered from 64 clinical samples including 9 urines, demonstrating this method could be used in different types of samples. For clinical samples, the results can be obtained within a time frame of 7 h 40 min to 10 h 40 min, while for isolates, the turnaround time was approximately 2 h shorter.
Conclusions
This method can serve as a versatile and convenient culture-free diagnostic method with the advantages of high sensitivity and accuracy.
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