Domanovich-Asor Tal, Motro Yair, Khalfin Boris, Craddock Hillary A, Peretz Avi, Moran-Gilad Jacob
MAGICAL Group, Department of Health Systems Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Clinical Microbiology Laboratory, Baruch Padeh Medical Center, Poriyah and Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Microorganisms. 2020 Dec 22;9(1):2. doi: 10.3390/microorganisms9010002.
Antimicrobial resistance (AMR) in is increasing and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to comprehensively analyze the resistome and phylogeny in order to characterize Israeli . Israeli isolates ( = 48) underwent antimicrobial susceptibility testing (AST) against five antimicrobials and WGS analysis. Literature review identified 111 mutations reported to correlate with phenotypic resistance to these antimicrobials. Analysis was conducted via our bioinformatics pipeline targeting point mutations in the relevant genes (, 23S , , and ) in order to assess genotype-to-phenotype correlation. Resistance rates of study isolates were as follows: clarithromycin 54%, metronidazole 31%, amoxicillin 10%, rifampicin 4%, and levofloxacin 2%. Genotype-to-phenotype correlation was inconsistent; for every analyzed gene at least one phenotypically susceptible isolate was found to have a mutation previously associated with resistance. This was also observed regarding mutations commonly used in commercial kits to diagnose AMR in cases. Furthermore, 11 novel point mutations associated with a resistant phenotype were detected. Analysis of a unique set of isolates demonstrates that inferring resistance phenotypes from WGS in remains challenging and should be optimized further.
幽门螺杆菌的抗菌药物耐药性(AMR)正在增加,可导致治疗失败和抗生素使用不当。本研究使用全基因组测序(WGS)全面分析幽门螺杆菌的耐药组和系统发育,以表征以色列幽门螺杆菌。对48株以色列幽门螺杆菌分离株进行了针对五种抗菌药物的药敏试验(AST)和WGS分析。文献综述确定了111个据报道与对这些抗菌药物的表型耐药相关的突变。通过我们的生物信息学流程针对相关基因(rpoB、23S rRNA、gyrA和parC)中的点突变进行分析,以评估基因型与表型的相关性。研究分离株的耐药率如下:克拉霉素54%,甲硝唑31%,阿莫西林10%,利福平4%,左氧氟沙星2%。基因型与表型的相关性不一致;对于每个分析的基因,至少发现一株表型敏感的分离株具有先前与耐药相关的突变。在用于诊断幽门螺杆菌病例中AMR的商业试剂盒中常用的突变方面也观察到了这一点。此外,还检测到11个与耐药表型相关的新的点突变。对一组独特的幽门螺杆菌分离株的分析表明,从WGS推断幽门螺杆菌的耐药表型仍然具有挑战性,需要进一步优化。