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Helicobacter pylori infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-genome Sequencing.

Abstract

Emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa 0.84, 95% CI: 0.67-1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa 0.90, 95% CI: 0.77-1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa = 0.76, 95% CI: 0.56-0.96). Previously identified mutations in the rpoB rifampicin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampicin resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates and our findings support the use of WGS for detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance.

Authors+Show Affiliations

Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY.Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.Biocomplexity Institute and Initiative, University of Virginia, Charlottesville, VA, USA.Provincial Public Health Laboratory, Eastern Health Microbiology Services, St. John's, New, Foundland and Labrador, Canada.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY. Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.Department of Medicine, Division of Gastroenterology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.Department of Pediatrics, Division of Gastroenterology and Nutrition, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY.Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY.Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY wszymcza@montefiore.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31801839

Citation

Saranathan, Rajagopalan, et al. "Helicobacter Pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage By Whole-genome Sequencing." Journal of Clinical Microbiology, 2019.
Saranathan R, Levi MH, Wattam AR, et al. Helicobacter pylori infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-genome Sequencing. J Clin Microbiol. 2019.
Saranathan, R., Levi, M. H., Wattam, A. R., Malek, A., Asare, E., Behin, D. S., ... Szymczak, W. A. (2019). Helicobacter pylori infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-genome Sequencing. Journal of Clinical Microbiology, doi:10.1128/JCM.01591-19.
Saranathan R, et al. Helicobacter Pylori Infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage By Whole-genome Sequencing. J Clin Microbiol. 2019 Dec 4; PubMed PMID: 31801839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Helicobacter pylori infections in the Bronx, New York: Surveying Antibiotic Susceptibility and Strain Lineage by Whole-genome Sequencing. AU - Saranathan,Rajagopalan, AU - Levi,Michael H, AU - Wattam,Alice R, AU - Malek,Adel, AU - Asare,Emmanuel, AU - Behin,Daniel S, AU - Pan,Debra H, AU - Jacobs,William R, AU - Szymczak,Wendy A, Y1 - 2019/12/04/ PY - 2019/12/6/entrez PY - 2019/12/6/pubmed PY - 2019/12/6/medline JF - Journal of clinical microbiology JO - J. Clin. Microbiol. N2 - Emergence of drug resistance in Helicobacter pylori has resulted in a greater need for susceptibility-guided treatment. While alleles associated with resistance to clarithromycin and levofloxacin have been defined, there are limited data regarding molecular mechanisms underlying resistance to other antimicrobials. Using H. pylori isolates from 42 clinical specimens, we compared phenotypic and whole genome sequencing (WGS)-based detection of resistance. Phenotypic resistance correlated with the presence of alleles of 23S rRNA (A2142G/A2143G) for clarithromycin (kappa 0.84, 95% CI: 0.67-1.0) and gyrA (N87I/N87K/D91Y/D91N/D91G/D99N) for levofloxacin (kappa 0.90, 95% CI: 0.77-1.0). Phenotypic resistance to amoxicillin in three isolates correlated with mutations in pbp1, pbp2, and/or pbp3 within coding regions near known amoxicillin binding motifs. All isolates were phenotypically susceptible to tetracycline, although four bore a mutation in 16S rRNA (A926G). For metronidazole, nonsense mutations and R16H substitutions in rdxA correlated with phenotypic resistance (kappa = 0.76, 95% CI: 0.56-0.96). Previously identified mutations in the rpoB rifampicin resistance-determining region (RRDR) were not present, but 14 novel mutations outside the RRDR were found in rifampicin resistant isolates. WGS also allowed for strain lineage determination, which may be important for future studies in associating precise MICs with specific resistance alleles. In summary, WGS allows for broad analyses of H. pylori isolates and our findings support the use of WGS for detection of clarithromycin and levofloxacin resistance. Additional studies are warranted to better define mutations conferring resistance to amoxicillin, tetracycline, and rifampin, but combinatorial analyses for rdxA gene truncations and R16H mutations have utility for determining metronidazole resistance. SN - 1098-660X UR - https://www.unboundmedicine.com/medline/citation/31801839/Helicobacter_pylori_infections_in_the_Bronx,_New_York:_Surveying_Antibiotic_Susceptibility_and_Strain_Lineage_by_Whole-genome_Sequencing L2 - http://jcm.asm.org/cgi/pmidlookup?view=long&pmid=31801839 DB - PRIME DP - Unbound Medicine ER -