WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel
Rapid developments in the field of whole genome sequencing (WGS) make in silico antimicrobial resistance (AMR) a target within reach. Campylobacter jejuni is a leading cause of foodborne infections in Israel with increasing rates of resistance. We applied WGS analysis to study the prevalence and gen...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-08-01
|
| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00365/full |
| _version_ | 1819051290563444736 |
|---|---|
| author | Assaf Rokney Lea Valinsky Katleen Vranckx Noa Feldman Vered Agmon Jacob Moran-Gilad Miriam Weinberger Miriam Weinberger |
| author_facet | Assaf Rokney Lea Valinsky Katleen Vranckx Noa Feldman Vered Agmon Jacob Moran-Gilad Miriam Weinberger Miriam Weinberger |
| author_sort | Assaf Rokney |
| collection | DOAJ |
| description | Rapid developments in the field of whole genome sequencing (WGS) make in silico antimicrobial resistance (AMR) a target within reach. Campylobacter jejuni is a leading cause of foodborne infections in Israel with increasing rates of resistance. We applied WGS analysis to study the prevalence and genetic basis of AMR in 263 C. jejuni human and veterinary representative isolates retrieved from a national collection during 2003–2012. We evaluated the prediction of phenotypic AMR from genomic data. Genomes were screened by the NCBI AMRFinderPlus and the BioNumerics tools for acquired AMR genes and point mutations. The results were compared to phenotypic resistance determined by broth microdilution. The most prevalent resistant determinants were the multi-drug efflux transporter gene cmeABC (100%), the tetracycline resistance tet(O) gene (82.1%), the quinolone resistance gyrA T861 point mutation (75.7%), and the aadE streptomycin resistance gene. A variety of 12 known β lactam resistance genes (blaOXA variants) were detected in 241 (92%) isolates, the most prevalent being blaOXA−193, blaOXA−461, and blaOXA−580 (56, 16, and 7%, respectively). Other aminoglycoside resistance genes and the macrolide resistance point mutation were rare (<1%). The overall correlation rate between WGS-based genotypic prediction and phenotypic resistance was 98.8%, sensitivity, specificity, positive, and negative predictive values being 98.0, 99.3, 99.1, and 98.5%, respectively. wgMLST-based phylogeny indicated a high level of clonality and clustering among the studied isolates. Closely related isolates that were part of a genetic cluster (single linkage distance ≤ 15 alleles) based on wgMLST phylogeny mostly shared a homogenous AMR determinant profile. This was observed in 18 of 20 (90.0%) clusters within clonal complex-21, suggesting clonal expansion of resistant isolates. Strong association to lineage was noted for the aadE gene and the various blaOXA genes. High resistance rates to tetracycline and quinolones and a low resistance rate to macrolides were detected among the Israeli C. jejuni isolates. While a high genotypic-phenotypic correlation was found, some resistance phenotypes could not be predicted by the presence of AMR determinants, and particularly not the level of resistance. WGS-based prediction of antimicrobial resistance in C. jejuni requires further optimization in order to integrate this approach in the routine workflow of public health laboratories for foodborne surveillance. |
| first_indexed | 2024-12-21T12:01:36Z |
| format | Article |
| id | doaj.art-295507571dac4881a5a974629eff43d5 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-21T12:01:36Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-295507571dac4881a5a974629eff43d52022-12-21T19:04:49ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-08-011010.3389/fcimb.2020.00365540111WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From IsraelAssaf Rokney0Lea Valinsky1Katleen Vranckx2Noa Feldman3Vered Agmon4Jacob Moran-Gilad5Miriam Weinberger6Miriam Weinberger7Central Government Laboratories, Israel Ministry of Health, Jerusalem, IsraelCentral Government Laboratories, Israel Ministry of Health, Jerusalem, IsraelApplied Maths NV, Sint-Martens-Latem, BelgiumCentral Government Laboratories, Israel Ministry of Health, Jerusalem, IsraelCentral Government Laboratories, Israel Ministry of Health, Jerusalem, IsraelDepartment of Health Systems Management, School of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Be'er Sheva, IsraelInfectious Diseases Unit, Shamir (Assaf Harofeh) Medical Center, Zerifin, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelRapid developments in the field of whole genome sequencing (WGS) make in silico antimicrobial resistance (AMR) a target within reach. Campylobacter jejuni is a leading cause of foodborne infections in Israel with increasing rates of resistance. We applied WGS analysis to study the prevalence and genetic basis of AMR in 263 C. jejuni human and veterinary representative isolates retrieved from a national collection during 2003–2012. We evaluated the prediction of phenotypic AMR from genomic data. Genomes were screened by the NCBI AMRFinderPlus and the BioNumerics tools for acquired AMR genes and point mutations. The results were compared to phenotypic resistance determined by broth microdilution. The most prevalent resistant determinants were the multi-drug efflux transporter gene cmeABC (100%), the tetracycline resistance tet(O) gene (82.1%), the quinolone resistance gyrA T861 point mutation (75.7%), and the aadE streptomycin resistance gene. A variety of 12 known β lactam resistance genes (blaOXA variants) were detected in 241 (92%) isolates, the most prevalent being blaOXA−193, blaOXA−461, and blaOXA−580 (56, 16, and 7%, respectively). Other aminoglycoside resistance genes and the macrolide resistance point mutation were rare (<1%). The overall correlation rate between WGS-based genotypic prediction and phenotypic resistance was 98.8%, sensitivity, specificity, positive, and negative predictive values being 98.0, 99.3, 99.1, and 98.5%, respectively. wgMLST-based phylogeny indicated a high level of clonality and clustering among the studied isolates. Closely related isolates that were part of a genetic cluster (single linkage distance ≤ 15 alleles) based on wgMLST phylogeny mostly shared a homogenous AMR determinant profile. This was observed in 18 of 20 (90.0%) clusters within clonal complex-21, suggesting clonal expansion of resistant isolates. Strong association to lineage was noted for the aadE gene and the various blaOXA genes. High resistance rates to tetracycline and quinolones and a low resistance rate to macrolides were detected among the Israeli C. jejuni isolates. While a high genotypic-phenotypic correlation was found, some resistance phenotypes could not be predicted by the presence of AMR determinants, and particularly not the level of resistance. WGS-based prediction of antimicrobial resistance in C. jejuni requires further optimization in order to integrate this approach in the routine workflow of public health laboratories for foodborne surveillance.https://www.frontiersin.org/article/10.3389/fcimb.2020.00365/fullCampylobacter jejuniantimicrobial resistanceantimicrobial-susceptibility testingbioinformaticswhole-genome sequencing |
| spellingShingle | Assaf Rokney Lea Valinsky Katleen Vranckx Noa Feldman Vered Agmon Jacob Moran-Gilad Miriam Weinberger Miriam Weinberger WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel Frontiers in Cellular and Infection Microbiology Campylobacter jejuni antimicrobial resistance antimicrobial-susceptibility testing bioinformatics whole-genome sequencing |
| title | WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel |
| title_full | WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel |
| title_fullStr | WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel |
| title_full_unstemmed | WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel |
| title_short | WGS-Based Prediction and Analysis of Antimicrobial Resistance in Campylobacter jejuni Isolates From Israel |
| title_sort | wgs based prediction and analysis of antimicrobial resistance in campylobacter jejuni isolates from israel |
| topic | Campylobacter jejuni antimicrobial resistance antimicrobial-susceptibility testing bioinformatics whole-genome sequencing |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00365/full |
| work_keys_str_mv | AT assafrokney wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT leavalinsky wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT katleenvranckx wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT noafeldman wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT veredagmon wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT jacobmorangilad wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT miriamweinberger wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael AT miriamweinberger wgsbasedpredictionandanalysisofantimicrobialresistanceincampylobacterjejuniisolatesfromisrael |