First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
Abstract 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 in...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Antimicrobial Resistance and Infection Control |
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| Online Access: | https://doi.org/10.1186/s13756-022-01101-2 |
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| author | Jupiter Marina Kabahita Joel Kabugo Francis Kakooza Isa Adam Ocung Guido Henry Byabajungu Joanitah Namutebi Maria Magdalene Namaganda Pius Lutaaya James Otim Fredrick Elishama Kakembo Stephen Kanyerezi Patricia Nabisubi Ivan Sserwadda George William Kasule Hasfah Nakato Kenneth Musisi Denis Oola Moses L. Joloba Gerald Mboowa |
| author_facet | Jupiter Marina Kabahita Joel Kabugo Francis Kakooza Isa Adam Ocung Guido Henry Byabajungu Joanitah Namutebi Maria Magdalene Namaganda Pius Lutaaya James Otim Fredrick Elishama Kakembo Stephen Kanyerezi Patricia Nabisubi Ivan Sserwadda George William Kasule Hasfah Nakato Kenneth Musisi Denis Oola Moses L. Joloba Gerald Mboowa |
| author_sort | Jupiter Marina Kabahita |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T05:17:37Z |
| format | Article |
| id | doaj.art-cad884e9023b41ef984fe5713b3076f0 |
| institution | Directory Open Access Journal |
| issn | 2047-2994 |
| language | English |
| last_indexed | 2024-12-12T05:17:37Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Antimicrobial Resistance and Infection Control |
| spelling | doaj.art-cad884e9023b41ef984fe5713b3076f02022-12-22T00:36:44ZengBMCAntimicrobial Resistance and Infection Control2047-29942022-05-011111810.1186/s13756-022-01101-2First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from UgandaJupiter Marina Kabahita0Joel Kabugo1Francis Kakooza2Isa Adam3Ocung Guido4Henry Byabajungu5Joanitah Namutebi6Maria Magdalene Namaganda7Pius Lutaaya8James Otim9Fredrick Elishama Kakembo10Stephen Kanyerezi11Patricia Nabisubi12Ivan Sserwadda13George William Kasule14Hasfah Nakato15Kenneth Musisi16Denis Oola17Moses L. Joloba18Gerald Mboowa19National Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryThe Infectious Diseases Institute, College of Heath Sciences, Makerere UniversityNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere UniversityNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryLira Regional Referral HospitalThe African Center of Excellence in Bioinformatics and Data-Intensive Sciences, The Infectious Diseases Institute, Makerere UniversityThe African Center of Excellence in Bioinformatics and Data-Intensive Sciences, The Infectious Diseases Institute, Makerere UniversityThe African Center of Excellence in Bioinformatics and Data-Intensive Sciences, The Infectious Diseases Institute, Makerere UniversityDepartment of Immunology and Molecular Biology, College of Health Sciences, Makerere UniversityNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryNational Tuberculosis Reference Laboratory/Supranational Reference LaboratoryAfrica Centres for Disease Control and Prevention, African Union CommissionAbstract 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.https://doi.org/10.1186/s13756-022-01101-2BedaquilineLinezolidClofazimineExtensively drug-resistant TB (XDR-TB)Whole-genome sequencing (WGS)Mycobacterium tuberculosis |
| spellingShingle | Jupiter Marina Kabahita Joel Kabugo Francis Kakooza Isa Adam Ocung Guido Henry Byabajungu Joanitah Namutebi Maria Magdalene Namaganda Pius Lutaaya James Otim Fredrick Elishama Kakembo Stephen Kanyerezi Patricia Nabisubi Ivan Sserwadda George William Kasule Hasfah Nakato Kenneth Musisi Denis Oola Moses L. Joloba Gerald Mboowa First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda Antimicrobial Resistance and Infection Control Bedaquiline Linezolid Clofazimine Extensively drug-resistant TB (XDR-TB) Whole-genome sequencing (WGS) Mycobacterium tuberculosis |
| 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 | Bedaquiline Linezolid Clofazimine Extensively drug-resistant TB (XDR-TB) Whole-genome sequencing (WGS) Mycobacterium tuberculosis |
| url | https://doi.org/10.1186/s13756-022-01101-2 |
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