Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Sonnenkalb, Lindsay; Carter, Joshua James; Barilar, Ivan; Battaglia, Simone; Borroni, Emanuele; Brandão, Angela Pires; Brankin, Alice; Cabibbe, Andrea Maurizio; Carter, Joshua A.; Cirillo, Daniela María; Claxton, Pauline; Clifton, David A.; Cohen, Ted; Coronel, Jorge; Crook, Derrick W.; Dreyer, Viola; Earle, Sarah G; Escuyer, Vincent; Ferrazoli, Lucilaine; Fowler, Philip; Gao, George F.; Gardy, Jennifer L.; Gharbia, Saheer E.; Ghisi, Kelen Teixeira; Ghodousi, Arash; Cruz, Ana Lúıza Gibertoni; Grandjean, Louis; Grazian, Clara; Groenheit, Ramona; Guthrie, Jennifer L.; He, Wencong; Hoffmann, Harald; Hoosdally, Sarah; Hunt, Martin; Iqbal, Zamin; Ismail, Nazir; Jarrett, Lisa; Joseph, Lavania; Jou, Ruwen; Kambli, Priti; Khot, R. S.; Knaggs, Jeff; Koch, Anastasia; Kohlerschmidt, Donna; Kouchaki, Samaneh; Lachapelle, Alexander; Lalvani, Ajit; Lapierre, Simon; Laurenson, Ian F.; Letcher, Brice; Lin, Wan-Hsuan; Liu, Chunfa; Liu, Dongxin; Malone, Kerri M.; Mandal, Ayan; Mansjö, Mikael; Matias, Daniela; Meintjes, Graeme; Mendes, Flávia de Freitas; Merker, Matthias; Mihalic, Marina; Millard, James; Miotto, Paolo; Mistry, Nerges; Moore, David; Musser, Kimberlee A.; Ngcamu, Dumisani; Hoang, Ngoc Nhung; Niemann, Stefan; Nilgiriwala, Kayzad; Nimmo, Camus; Okozi, Nana; Oliveira, Rosângela Siqueira de; Omar, Shaheed Vally; Paton, Nicholas I.; Peto, Timothy E. A.; Pinhata, Juliana Maira Watanabe; Plesnik, Sara; Puyén, Zully M.; Rabodoarivelo, Marie Sylvianne; Rakotosamimanana, Niaina; Rancoita, Paola Mv; Rathod, Priti; Rodger, Gillian; Rodrigues, Camilla; Rodwell, Timothy C.; Roohi, Eaysha; Santos-Lázaro, David; Shah, Sanchi; Köhl, Thomas; Smith, Grace; Solano, Walter; Spitaleri, Andrea; Supply, Philip; Surve, Utkarsha; Tahseen, Sabira; Thuong, Nguyen Thuy Thuong; Thwaites, Guy; Todt, Katharina; Trovato, Alberto; Utpatel, Christian; Rie, Annelies Van; Vijay, Srinivasan; Walker, Timothy M.; Walker, Sarah; Warren, Robin M.; Werngren, Jim; Wijkander, Maria; Wilkinson, Robert J.; Wilson, Daniel J.; Wintringer, Penelope; Yu, Xuan; Yang, Yang; Zhao, Yanlin; Yao, Shen-Yuan; Zhu, Baoli

doi:10.1016/s2666-5247(23)00002-2

Cited by 22 publications

(10 citation statements)

References 26 publications

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“…We found phenotype-genotype discrepancies for two isolates (#6242 and #6466) with a phenotype of BDQ resistance (Table 1, Table S1) that was not confirmed with genotypic prediction. The other four isolates phenotypically resistant to BDQ harbored mutations in the Rv0678 gene (G66E, S68G, and 193delG) conferring resistance, as described by Sonnenkalb et al [24]. Furthermore, the deletion 193delG in the Rv0678 gene conferred cross-resistance between BDQ and CFZ in isolate #1561; this cross-resistance was confirmed phenotypically.…”

Section: Comparison Of Phenotypic Drug Susceptibility Testing and Gen...supporting

confidence: 65%

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Auganova,

Atavliyeva,

Amirgazin

et al. 2023

Antibiotics

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Kazakhstan ranks among the countries with the highest number of MDR-TB patients per 100,000 population worldwide. The successful transmission of local MDR strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to disease control. In this study, we employed whole-genome sequencing to examine drug resistance, compensatory mutations, population structure, and transmission patterns in a sample of 24 clinical isolates of L2/Beijing Mtb collected in Astana, Kazakhstan between 2021 and 2022. The genotypic prediction of Mtb susceptibility to anti-TB agents was consistent with the phenotypic susceptibility, except for bedaquiline. An analysis of resistance-associated genes characterized most of the isolates as pre-extensively drug-resistant tuberculosis (pre-XDR-TB) (n = 15; 62.5%). The phylogenetic analysis grouped the isolates into four transmission clusters; the dominant cluster was assigned to the “aggressive” Central Asia outbreak (CAO) clade of L2/Beijing (n = 15; 62.5%). Thirteen mutations with putative compensatory effects were observed exclusively in Mtb isolates containing the rpoB S450L mutation. The putative compensatory mutations had a stabilizing effect on RpoABC protein stability and dynamics. The high prevalence of the CAO clade in the population structure of Mtb may explain the rapid spread of MDR-TB in Kazakhstan.

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Section: Comparison Of Phenotypic Drug Susceptibility Testing and Gen...supporting

confidence: 65%

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Auganova,

Atavliyeva,

Amirgazin

et al. 2023

Antibiotics

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“…Both mutations have been reported before. 33 , 34 Of these six patients only one was treated before for MDR-TB. Five of these patients received clofazimine (CFZ) during their current treatment.…”

Section: Resultsmentioning

confidence: 99%

Prison as a driver of recent transmissions of multidrug-resistant tuberculosis in Callao, Peru: a cross-sectional study

Utpatel,

Zavaleta,

Rojas-Bolivar

et al. 2024

The Lancet Regional Health - Americas

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“…Only Rv0678 S53P is marked as uncertain significance in catalog of mutation. Mutation Rv0678 А36Т is not listed in the catalog but previously was described as associated with a bedaquiline-resistant phenotype (low confidence) ( 17 ). It is important to note that the Rv0678 S53P mutation was identified in Mtb isolates from BDQ-naive patients, while the other patient had received BDQ for 13–36 months ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of genetic determinants of bedaquiline resistance in Mycobacterium tuberculosis in Ural region, Russia

Umpeleva,

Chetverikova,

Belyaev

et al. 2024

Microbiol Spectr

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Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Cited by 22 publications

References 26 publications

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Prison as a driver of recent transmissions of multidrug-resistant tuberculosis in Callao, Peru: a cross-sectional study

Identification of genetic determinants of bedaquiline resistance in Mycobacterium tuberculosis in Ural region, Russia

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