Cargando…

First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda

BACKGROUND: Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including...

Descripción completa

Detalles Bibliográficos
Autores principales: Kabahita, Jupiter Marina, Kabugo, Joel, Kakooza, Francis, Adam, Isa, Guido, Ocung, Byabajungu, Henry, Namutebi, Joanitah, Namaganda, Maria Magdalene, Lutaaya, Pius, Otim, James, Kakembo, Fredrick Elishama, Kanyerezi, Stephen, Nabisubi, Patricia, Sserwadda, Ivan, Kasule, George William, Nakato, Hasfah, Musisi, Kenneth, Oola, Denis, Joloba, Moses L., Mboowa, Gerald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102340/
https://www.ncbi.nlm.nih.gov/pubmed/35550202
http://dx.doi.org/10.1186/s13756-022-01101-2
_version_ 1784707305438183424
author Kabahita, Jupiter Marina
Kabugo, Joel
Kakooza, Francis
Adam, Isa
Guido, Ocung
Byabajungu, Henry
Namutebi, Joanitah
Namaganda, Maria Magdalene
Lutaaya, Pius
Otim, James
Kakembo, Fredrick Elishama
Kanyerezi, Stephen
Nabisubi, Patricia
Sserwadda, Ivan
Kasule, George William
Nakato, Hasfah
Musisi, Kenneth
Oola, Denis
Joloba, Moses L.
Mboowa, Gerald
author_facet Kabahita, Jupiter Marina
Kabugo, Joel
Kakooza, Francis
Adam, Isa
Guido, Ocung
Byabajungu, Henry
Namutebi, Joanitah
Namaganda, Maria Magdalene
Lutaaya, Pius
Otim, James
Kakembo, Fredrick Elishama
Kanyerezi, Stephen
Nabisubi, Patricia
Sserwadda, Ivan
Kasule, George William
Nakato, Hasfah
Musisi, Kenneth
Oola, Denis
Joloba, Moses L.
Mboowa, Gerald
author_sort Kabahita, Jupiter Marina
collection PubMed
description BACKGROUND: Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including improper treatment regimens and failure to complete the treatment course which may be due to an unstable supply or a lack of access to treatment, as well as patient noncompliance. METHODS: Two sputa samples were collected from Xpert MTB/RIF® assay-diagnosed multi-drug resistant tuberculosis (MDR-TB) patient at Lira regional referral hospital in northern Uganda between 2020 and 2021 for comprehensive routine mycobacterial species identification and drug susceptibility testing using culture-based methods. Detection of drug resistance-conferring genes was subsequently performed using whole-genome sequencing with Illumina MiSeq platform at the TB Supranational Reference Laboratory in Uganda. RESULTS: In both isolates, extensively drug-resistant TB (XDR-TB) was identified including resistance to Isoniazid (katG p.Ser315Thr), Rifampicin (rpoB p.Ser450Leu), Moxifloxacin (gyrA p.Asp94Gly), Bedaquiline (Rv0678 Glu49fs), Clofazimine (Rv0678 Glu49fs), Linezolid (rplC Cys154Arg), and Ethionamide (ethA c.477del). Further analysis of these two high quality genomes revealed that this 32 years-old patient was infected with the Latin American Mediterranean TB strain (LAM). CONCLUSIONS: This is the first identification of extensively drug-resistant Mycobacterium tuberculosis clinical isolates with bedaquiline, linezolid and clofazimine resistance from Uganda. These acquired resistances were because of non-adherence as seen in the patient’s clinical history. Our study also strongly highlights the importance of combating DR-TB in Africa through implementing next generation sequencing that can test resistance to all drugs while providing a faster turnaround time. This can facilitate timely clinical decisions in managing MDR-TB patients with non-adherence or lost to follow-up. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13756-022-01101-2.
format Online
Article
Text
id pubmed-9102340
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-91023402022-05-14 First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda Kabahita, Jupiter Marina Kabugo, Joel Kakooza, Francis Adam, Isa Guido, Ocung Byabajungu, Henry Namutebi, Joanitah Namaganda, Maria Magdalene Lutaaya, Pius Otim, James Kakembo, Fredrick Elishama Kanyerezi, Stephen Nabisubi, Patricia Sserwadda, Ivan Kasule, George William Nakato, Hasfah Musisi, Kenneth Oola, Denis Joloba, Moses L. Mboowa, Gerald Antimicrob Resist Infect Control Short Report BACKGROUND: Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including improper treatment regimens and failure to complete the treatment course which may be due to an unstable supply or a lack of access to treatment, as well as patient noncompliance. METHODS: Two sputa samples were collected from Xpert MTB/RIF® assay-diagnosed multi-drug resistant tuberculosis (MDR-TB) patient at Lira regional referral hospital in northern Uganda between 2020 and 2021 for comprehensive routine mycobacterial species identification and drug susceptibility testing using culture-based methods. Detection of drug resistance-conferring genes was subsequently performed using whole-genome sequencing with Illumina MiSeq platform at the TB Supranational Reference Laboratory in Uganda. RESULTS: In both isolates, extensively drug-resistant TB (XDR-TB) was identified including resistance to Isoniazid (katG p.Ser315Thr), Rifampicin (rpoB p.Ser450Leu), Moxifloxacin (gyrA p.Asp94Gly), Bedaquiline (Rv0678 Glu49fs), Clofazimine (Rv0678 Glu49fs), Linezolid (rplC Cys154Arg), and Ethionamide (ethA c.477del). Further analysis of these two high quality genomes revealed that this 32 years-old patient was infected with the Latin American Mediterranean TB strain (LAM). CONCLUSIONS: This is the first identification of extensively drug-resistant Mycobacterium tuberculosis clinical isolates with bedaquiline, linezolid and clofazimine resistance from Uganda. These acquired resistances were because of non-adherence as seen in the patient’s clinical history. Our study also strongly highlights the importance of combating DR-TB in Africa through implementing next generation sequencing that can test resistance to all drugs while providing a faster turnaround time. This can facilitate timely clinical decisions in managing MDR-TB patients with non-adherence or lost to follow-up. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13756-022-01101-2. BioMed Central 2022-05-12 /pmc/articles/PMC9102340/ /pubmed/35550202 http://dx.doi.org/10.1186/s13756-022-01101-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Kabahita, Jupiter Marina
Kabugo, Joel
Kakooza, Francis
Adam, Isa
Guido, Ocung
Byabajungu, Henry
Namutebi, Joanitah
Namaganda, Maria Magdalene
Lutaaya, Pius
Otim, James
Kakembo, Fredrick Elishama
Kanyerezi, Stephen
Nabisubi, Patricia
Sserwadda, Ivan
Kasule, George William
Nakato, Hasfah
Musisi, Kenneth
Oola, Denis
Joloba, Moses L.
Mboowa, Gerald
First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
title First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
title_full First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
title_fullStr First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
title_full_unstemmed First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
title_short First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
title_sort first report of whole-genome analysis of an extensively drug-resistant mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from uganda
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102340/
https://www.ncbi.nlm.nih.gov/pubmed/35550202
http://dx.doi.org/10.1186/s13756-022-01101-2
work_keys_str_mv AT kabahitajupitermarina firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT kabugojoel firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT kakoozafrancis firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT adamisa firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT guidoocung firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT byabajunguhenry firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT namutebijoanitah firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT namagandamariamagdalene firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT lutaayapius firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT otimjames firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT kakembofredrickelishama firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT kanyerezistephen firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT nabisubipatricia firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT sserwaddaivan firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT kasulegeorgewilliam firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT nakatohasfah firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT musisikenneth firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT ooladenis firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT jolobamosesl firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda
AT mboowagerald firstreportofwholegenomeanalysisofanextensivelydrugresistantmycobacteriumtuberculosisclinicalisolatewithbedaquilinelinezolidandclofazimineresistancefromuganda