Prediction of Drug Resistance Profile of Multidrug-resistant Mycobacterium Tuberculosis (MDR-MTB) Isolates from Newly Diagnosed Case by Whole Genome Sequencing (WGS): a Study from a High Tuberculosis Burden Country

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2022 May 27

PMID 35624432

Authors

Wenwen Sun

Xuwei Gui

Zheyuan Wu

Yangyi Zhang

Liping Yan

Affiliations

Soon will be listed here.

Abstract

Objectives: Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China.

Methods: We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS.

Results: The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd.

Conclusions: WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.

Citing Articles

Cystatin F Depletion in -Infected Macrophages Improves Cathepsin C/Granzyme B-Driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.

Mandal M, Pires D, Calado M, Azevedo-Pereira J, Anes E Int J Mol Sci. 2024; 25(15).

PMID: 39125711 PMC: 11311260. DOI: 10.3390/ijms25158141.

Discordance Between Phenotypic and WGS-Based Drug Susceptibility Testing Results for Some Anti-Tuberculosis Drugs: A Snapshot Study of Paired Isolates with Small Genetic Distance.

Sadovska D, Nodieva A, Pole I, Viksna A, kimsis J, Ozere I Infect Drug Resist. 2024; 17:3289-3307.

PMID: 39108991 PMC: 11300831. DOI: 10.2147/IDR.S468997.

Evaluation of genetic correlation with fluoroquinolones resistance in rifampicin-resistant Mycobacterium tuberculosis isolates.

Teng C, Li L, Su D, Li H, Zhao B, Xia H Heliyon. 2024; 10(11):e31959.

PMID: 38868072 PMC: 11167346. DOI: 10.1016/j.heliyon.2024.e31959.

Whole Genome Sequencing of Mycobacterium tuberculosis under routine conditions in a high-burden area of multidrug-resistant tuberculosis in Peru.

Puyen Z, Santos-Lazaro D, Vigo A, Cotrina V, Ruiz-Nizama N, Alarcon M PLoS One. 2024; 19(6):e0304130.

PMID: 38861531 PMC: 11166294. DOI: 10.1371/journal.pone.0304130.

Mutations in the promoter region of methionine transporter gene (Rv3253c) confer -aminosalicylic acid (PAS) resistance in .

Zhang Y, Wang S, Chen X, Cui P, Chen J, Zhang W mBio. 2024; 15(2):e0207323.

PMID: 38179948 PMC: 10865796. DOI: 10.1128/mbio.02073-23.

References

Luna-Herrera J, Martinez-Cabrera G, Parra-Maldonado R, Enciso-Moreno J, Torres-Lopez J, Quesada-Pascual F . Use of receiver operating characteristic curves to assess the performance of a microdilution assay for determination of drug susceptibility of clinical isolates of Mycobacterium tuberculosis. Eur J Clin Microbiol Infect Dis. 2003; 22(1):21-7. DOI: 10.1007/s10096-002-0855-5. View

Yang C, Lu L, Warren J, Wu J, Jiang Q, Zuo T . Internal migration and transmission dynamics of tuberculosis in Shanghai, China: an epidemiological, spatial, genomic analysis. Lancet Infect Dis. 2018; 18(7):788-795. PMC: 6035060. DOI: 10.1016/S1473-3099(18)30218-4. View

Gillespie S . Evolution of drug resistance in Mycobacterium tuberculosis: clinical and molecular perspective. Antimicrob Agents Chemother. 2002; 46(2):267-74. PMC: 127054. DOI: 10.1128/AAC.46.2.267-274.2002. View

Ranzani O, Rodrigues L, Bombarda S, Minto C, Waldman E, Carvalho C . Long-term survival and cause-specific mortality of patients newly diagnosed with tuberculosis in São Paulo state, Brazil, 2010-15: a population-based, longitudinal study. Lancet Infect Dis. 2019; 20(1):123-132. PMC: 6928568. DOI: 10.1016/S1473-3099(19)30518-3. View

Lee J, Armstrong D, Ssengooba W, Park J, Yu Y, Mumbowa F . Sensititre MYCOTB MIC plate for testing Mycobacterium tuberculosis susceptibility to first- and second-line drugs. Antimicrob Agents Chemother. 2013; 58(1):11-8. PMC: 3910714. DOI: 10.1128/AAC.01209-13. View

Liu Q, Ma A, Wei L, Pang Y, Wu B, Luo T . China's tuberculosis epidemic stems from historical expansion of four strains of Mycobacterium tuberculosis. Nat Ecol Evol. 2018; 2(12):1982-1992. PMC: 6295914. DOI: 10.1038/s41559-018-0680-6. View

Machado D, Perdigao J, Ramos J, Couto I, Portugal I, Ritter C . High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations. J Antimicrob Chemother. 2013; 68(8):1728-32. DOI: 10.1093/jac/dkt090. View

Sirgel F, Warren R, Bottger E, Klopper M, Victor T, van Helden P . The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks. PLoS One. 2013; 8(3):e59414. PMC: 3602005. DOI: 10.1371/journal.pone.0059414. View

Mathys V, Wintjens R, Lefevre P, Bertout J, Singhal A, Kiass M . Molecular genetics of para-aminosalicylic acid resistance in clinical isolates and spontaneous mutants of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2009; 53(5):2100-9. PMC: 2681553. DOI: 10.1128/AAC.01197-08. View

10.

Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E . Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet. 2015; 47(3):242-9. PMC: 11044984. DOI: 10.1038/ng.3195. View

11.

Coll F, Phelan J, Hill-Cawthorne G, Nair M, Mallard K, Ali S . Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis. Nat Genet. 2018; 50(2):307-316. DOI: 10.1038/s41588-017-0029-0. View

12.

Shea J, Halse T, Lapierre P, Shudt M, Kohlerschmidt D, Van Roey P . Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State. J Clin Microbiol. 2017; 55(6):1871-1882. PMC: 5442544. DOI: 10.1128/JCM.00298-17. View

13.

Georghiou S, Magana M, Garfein R, Catanzaro D, Catanzaro A, Rodwell T . Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review. PLoS One. 2012; 7(3):e33275. PMC: 3315572. DOI: 10.1371/journal.pone.0033275. View

14.

Kardan-Yamchi J, Kazemian H, Battaglia S, Abtahi H, Rahimi Foroushani A, Hamzelou G . Whole Genome Sequencing Results Associated with Minimum Inhibitory Concentrations of 14 Anti-Tuberculosis Drugs among Rifampicin-Resistant Isolates of from Iran. J Clin Med. 2020; 9(2). PMC: 7073636. DOI: 10.3390/jcm9020465. View

15.

Vilcheze C, Jacobs Jr W . The mechanism of isoniazid killing: clarity through the scope of genetics. Annu Rev Microbiol. 2007; 61:35-50. DOI: 10.1146/annurev.micro.61.111606.122346. View

16.

Pankhurst L, Del Ojo Elias C, Votintseva A, Walker T, Cole K, Davies J . Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. Lancet Respir Med. 2015; 4(1):49-58. PMC: 4698465. DOI: 10.1016/S2213-2600(15)00466-X. View

17.

Marsili L, Pasqualucci C, Vigevani A, Gioia B, Schioppacassi G, Oronzo G . New rifamycins modified at positions 3 and 4. Synthesis, structure and biological evaluation. J Antibiot (Tokyo). 1981; 34(8):1033-8. DOI: 10.7164/antibiotics.34.1033. View

18.

Zignol M, Dean A, Alikhanova N, Andres S, Cabibbe A, Cirillo D . Population-based resistance of Mycobacterium tuberculosis isolates to pyrazinamide and fluoroquinolones: results from a multicountry surveillance project. Lancet Infect Dis. 2016; 16(10):1185-1192. PMC: 5030278. DOI: 10.1016/S1473-3099(16)30190-6. View

19.

Genestet C, Hodille E, Berland J, Ginevra C, Bryant J, Ader F . Whole-genome sequencing in drug susceptibility testing of Mycobacterium tuberculosis in routine practice in Lyon, France. Int J Antimicrob Agents. 2020; 55(4):105912. DOI: 10.1016/j.ijantimicag.2020.105912. View

20.

Angeby K, Jureen P, Kahlmeter G, Hoffner S, Schon T . Challenging a dogma: antimicrobial susceptibility testing breakpoints for Mycobacterium tuberculosis. Bull World Health Organ. 2012; 90(9):693-8. PMC: 3442398. DOI: 10.2471/BLT.11.096644. View