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. 2022 May 12;11(1):68.
doi: 10.1186/s13756-022-01101-2.

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

Jupiter Marina Kabahita  1 , Joel Kabugo  1 , Francis Kakooza  2 , Isa Adam  1 , Ocung Guido  1 , Henry Byabajungu  1 , Joanitah Namutebi  1 , Maria Magdalene Namaganda  3 , Pius Lutaaya  1 , James Otim  4 , Fredrick Elishama Kakembo  5 , Stephen Kanyerezi  5 , Patricia Nabisubi  5 , Ivan Sserwadda  3 , George William Kasule  1 , Hasfah Nakato  1 , Kenneth Musisi  1 , Denis Oola  1 , Moses L Joloba  1   3 , Gerald Mboowa  6   7
Affiliations

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

Jupiter Marina Kabahita et al. Antimicrob Resist Infect Control. .

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.

Keywords: Bedaquiline; Clofazimine; Extensively drug-resistant TB (XDR-TB); Linezolid; Mycobacterium tuberculosis; Whole-genome sequencing (WGS).

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Phylogenetic relationship between the two XDR samples and other 169 sequences from Uganda
See this image and copyright information in PMC

References

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