Cargando…

Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania

BACKGROUND: Reliable phenotypic antimicrobial susceptibility testing can be a challenge in clinical settings in low- and middle-income countries. WGS is a promising approach to enhance current capabilities. AIM: To study diversity and resistance determinants and to predict and compare resistance pat...

Descripción completa

Detalles Bibliográficos
Autores principales: Kumburu, Happiness H, Sonda, Tolbert, van Zwetselaar, Marco, Leekitcharoenphon, Pimlapas, Lukjancenko, Oksana, Mmbaga, Blandina T, Alifrangis, Michael, Lund, Ole, Aarestrup, Frank M, Kibiki, Gibson S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524488/
https://www.ncbi.nlm.nih.gov/pubmed/30843063
http://dx.doi.org/10.1093/jac/dkz055
_version_ 1783419566939963392
author Kumburu, Happiness H
Sonda, Tolbert
van Zwetselaar, Marco
Leekitcharoenphon, Pimlapas
Lukjancenko, Oksana
Mmbaga, Blandina T
Alifrangis, Michael
Lund, Ole
Aarestrup, Frank M
Kibiki, Gibson S
author_facet Kumburu, Happiness H
Sonda, Tolbert
van Zwetselaar, Marco
Leekitcharoenphon, Pimlapas
Lukjancenko, Oksana
Mmbaga, Blandina T
Alifrangis, Michael
Lund, Ole
Aarestrup, Frank M
Kibiki, Gibson S
author_sort Kumburu, Happiness H
collection PubMed
description BACKGROUND: Reliable phenotypic antimicrobial susceptibility testing can be a challenge in clinical settings in low- and middle-income countries. WGS is a promising approach to enhance current capabilities. AIM: To study diversity and resistance determinants and to predict and compare resistance patterns from WGS data of Acinetobacter baumannii with phenotypic results from classical microbiological testing at a tertiary care hospital in Tanzania. METHODS AND RESULTS: MLST using Pasteur/Oxford schemes yielded eight different STs from each scheme. Of the eight, two STs were identified to be global clones 1 (n = 4) and 2 (n = 1) as per the Pasteur scheme. Resistance testing using classical microbiology determined between 50% and 92.9% resistance across all drugs. Percentage agreement between phenotypic and genotypic prediction of resistance ranged between 57.1% and 100%, with coefficient of agreement (κ) between 0.05 and 1. Seven isolates harboured mutations at significant loci (S81L in gyrA and S84L in parC). A number of novel plasmids were detected, including pKCRI-309C-1 (219000 bp) carrying 10 resistance genes, pKCRI-43-1 (34935 bp) carrying two resistance genes and pKCRI-49-1 (11681 bp) and pKCRI-28-1 (29606 bp), each carrying three resistance genes. New ampC alleles detected included ampC-69, ampC-70 and ampC-71. Global clone 1 and 2 isolates were found to harbour ISAba1 directly upstream of the ampC gene. Finally, SNP-based phylogenetic analysis of the A. baumannii isolates revealed closely related isolates in three clusters. CONCLUSIONS: The validity of the use of WGS in the prediction of phenotypic resistance can be appreciated, but at this stage is not sufficient for it to replace conventional antimicrobial susceptibility testing in our setting.
format Online
Article
Text
id pubmed-6524488
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-65244882019-05-21 Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania Kumburu, Happiness H Sonda, Tolbert van Zwetselaar, Marco Leekitcharoenphon, Pimlapas Lukjancenko, Oksana Mmbaga, Blandina T Alifrangis, Michael Lund, Ole Aarestrup, Frank M Kibiki, Gibson S J Antimicrob Chemother Original Research BACKGROUND: Reliable phenotypic antimicrobial susceptibility testing can be a challenge in clinical settings in low- and middle-income countries. WGS is a promising approach to enhance current capabilities. AIM: To study diversity and resistance determinants and to predict and compare resistance patterns from WGS data of Acinetobacter baumannii with phenotypic results from classical microbiological testing at a tertiary care hospital in Tanzania. METHODS AND RESULTS: MLST using Pasteur/Oxford schemes yielded eight different STs from each scheme. Of the eight, two STs were identified to be global clones 1 (n = 4) and 2 (n = 1) as per the Pasteur scheme. Resistance testing using classical microbiology determined between 50% and 92.9% resistance across all drugs. Percentage agreement between phenotypic and genotypic prediction of resistance ranged between 57.1% and 100%, with coefficient of agreement (κ) between 0.05 and 1. Seven isolates harboured mutations at significant loci (S81L in gyrA and S84L in parC). A number of novel plasmids were detected, including pKCRI-309C-1 (219000 bp) carrying 10 resistance genes, pKCRI-43-1 (34935 bp) carrying two resistance genes and pKCRI-49-1 (11681 bp) and pKCRI-28-1 (29606 bp), each carrying three resistance genes. New ampC alleles detected included ampC-69, ampC-70 and ampC-71. Global clone 1 and 2 isolates were found to harbour ISAba1 directly upstream of the ampC gene. Finally, SNP-based phylogenetic analysis of the A. baumannii isolates revealed closely related isolates in three clusters. CONCLUSIONS: The validity of the use of WGS in the prediction of phenotypic resistance can be appreciated, but at this stage is not sufficient for it to replace conventional antimicrobial susceptibility testing in our setting. Oxford University Press 2019-06 2019-03-06 /pmc/articles/PMC6524488/ /pubmed/30843063 http://dx.doi.org/10.1093/jac/dkz055 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Kumburu, Happiness H
Sonda, Tolbert
van Zwetselaar, Marco
Leekitcharoenphon, Pimlapas
Lukjancenko, Oksana
Mmbaga, Blandina T
Alifrangis, Michael
Lund, Ole
Aarestrup, Frank M
Kibiki, Gibson S
Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania
title Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania
title_full Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania
title_fullStr Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania
title_full_unstemmed Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania
title_short Using WGS to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in MDR Acinetobacter baumannii in Tanzania
title_sort using wgs to identify antibiotic resistance genes and predict antimicrobial resistance phenotypes in mdr acinetobacter baumannii in tanzania
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524488/
https://www.ncbi.nlm.nih.gov/pubmed/30843063
http://dx.doi.org/10.1093/jac/dkz055
work_keys_str_mv AT kumburuhappinessh usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT sondatolbert usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT vanzwetselaarmarco usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT leekitcharoenphonpimlapas usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT lukjancenkooksana usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT mmbagablandinat usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT alifrangismichael usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT lundole usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT aarestrupfrankm usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania
AT kibikigibsons usingwgstoidentifyantibioticresistancegenesandpredictantimicrobialresistancephenotypesinmdracinetobacterbaumanniiintanzania