MDR and Pre-XDR Clinical Mycobacterium tuberculosis Beijing Strains: Assessment of Virulence and Host Cytokine Response in Mice Infectious Model

Mycobacterium tuberculosis Beijing genotype associated with drug resistance is a growing public health problem worldwide. The aim of this study was the assessment of virulence for C57BL/6 mice after infection by clinical M. tuberculosis strains 267/47 and 120/26, which belong to the modern sublineages B0/W148 and Central Asia outbreak of the Beijing genotype, respectively. The sublineages were identified by the analysis of the strains’ whole-genomes. The strains 267/47 and 120/26 were characterized as agents of pre-extensively drug-resistant (pre-XDR) and multidrug-resistant (MDR) tuberculosis, respectively. Both clinical strains were slow-growing in 7H9 broth compared to the M. tuberculosis H37Rv strain. The survival rates of C57BL/6 mice infected by 267/47, 120/26, and H37Rv on the 150th day postinfection were 10%, 40%, and 70%, respectively. Mycobacterial load in the lungs, spleen, and liver was higher and histopathological changes were more expressed for mice infected by the 267/47 strain compared to those infected by the 120/26 and H37Rv strains. The cytokine response in the lungs of C57BL/6 mice after infection with the 267/47, 120/26, and H37Rv strains was different. Notably, proinflammatory cytokine genes Il-1α, Il-6, Il-7, and Il-17, as well as anti-inflammatory genes Il-6 and Il-13, were downregulated after an infection caused by the 267/47 strain compared to those after infection with the H37Rv strain.

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A genome-wide analysis of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis Beijing genotype

Molecular Genetics and Genomics ◽

10.1007/s00438-013-0758-4 ◽

2013 ◽

Vol 288 (9) ◽

pp. 425-436 ◽

Cited By ~ 10

Author(s):

Wei Wu ◽

Huajun Zheng ◽

Lu Zhang ◽

Zilu Wen ◽

Shulin Zhang ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Multidrug Resistant ◽

Beijing Genotype ◽

Drug Resistant ◽

Genome Wide Analysis ◽

Extensively Drug Resistant ◽

Genome Wide ◽

A Genome ◽

Resistant Strains ◽

Drug Resistant Strains

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Beijing genotype of Mycobacterium tuberculosis is significantly associated with linezolid resistance in multidrug-resistant and extensively drug-resistant tuberculosis in China

International Journal of Antimicrobial Agents ◽

10.1016/j.ijantimicag.2013.12.007 ◽

2014 ◽

Vol 43 (3) ◽

pp. 231-235 ◽

Cited By ~ 40

Author(s):

Zhijian Zhang ◽

Yu Pang ◽

Yufeng Wang ◽

Changting Liu ◽

Yanlin Zhao

Keyword(s):

Mycobacterium Tuberculosis ◽

Multidrug Resistant ◽

Beijing Genotype ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Linezolid Resistance ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant

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Genotyping, Assessment of Virulence and Antibacterial Resistance of the Rostov Strain of Mycobacterium tuberculosis Attributed to the Central Asia Outbreak Clade

Pathogens ◽

10.3390/pathogens9050335 ◽

2020 ◽

Vol 9 (5) ◽

pp. 335 ◽

Cited By ~ 1

Author(s):

Mikhail V. Fursov ◽

Egor A. Shitikov ◽

Julia A. Bespyatykh ◽

Alexander G. Bogun ◽

Angelina A. Kislichkina ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Central Asia ◽

Bacterial Load ◽

Public Health Problem ◽

Laboratory Strain ◽

Beijing Genotype ◽

Central Asian ◽

H37rv Strain ◽

Weight Analysis ◽

Virulent Phenotype

The Central Asia Outbreak (CAO) clade is a growing public health problem for Central Asian countries. Members of the clade belong to the narrow branch of the Mycobacterium tuberculosis Beijing genotype and are characterized by multidrug resistance and increased transmissibility. The Rostov strain of M. tuberculosis isolated in Russia and attributed to the CAO clade based on PCR-assay and whole genome sequencing and the laboratory strain H37Rv were selected to evaluate the virulence on C57Bl/6 mice models by intravenous injection. All mice infected with the Rostov strain succumbed to death within a 48-day period, while more than half of the mice infected by the H37Rv strain survived within a 90-day period. Mice weight analysis revealed irreversible and severe depletion of animals infected with the Rostov strain compared to H37Rv. The histological investigation of lung and liver tissues of mice on the 30th day after injection of mycobacterial bacilli showed that the pattern of pathological changes generated by two strains were different. Moreover, bacterial load in the liver and lungs was higher for the Rostov strain infection. In conclusion, our data demonstrate that the drug-resistant Rostov strain exhibits a highly virulent phenotype which can be partly explained by the CAO-specific mutations.

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RNA expression analysis of efflux pump genes in clinical isolates of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis

10.26226/morressier.56d5ba2cd462b80296c94d42 ◽

2016 ◽

Author(s):

Hee Joo Lee

Keyword(s):

Mycobacterium Tuberculosis ◽

Expression Analysis ◽

Efflux Pump ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Rna Expression ◽

Drug Resistant ◽

Extensively Drug Resistant

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Metabolic profiles of multidrug resistant and extensively drug resistant Mycobacterium tuberculosis unveiled by metabolomics

Tuberculosis ◽

10.1016/j.tube.2020.102043 ◽

2021 ◽

Vol 126 ◽

pp. 102043

Author(s):

Amanda Mendes Rêgo ◽

Duanne Alves da Silva ◽

Nicole Victor Ferreira ◽

Lucindo Cardoso de Pina ◽

Joseph A.M. Evaristo ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Multidrug Resistant ◽

Metabolic Profiles ◽

Drug Resistant ◽

Extensively Drug Resistant

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In Vitro Synergism Testing of Three Antimicrobial Agents against Multidrug- Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis by Checkerboard Method

Journal of Molecular Pharmaceutics & Organic Process Research ◽

10.4172/2329-9053.1000123 ◽

2015 ◽

Vol 03 (01) ◽

Author(s):

Liping Yan Linlin Zhang

Keyword(s):

Mycobacterium Tuberculosis ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Drug Resistant ◽

Extensively Drug Resistant

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Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00165-18 ◽

2018 ◽

Vol 62 (8) ◽

Cited By ~ 18

Author(s):

Zhaojing Zong ◽

Wei Jing ◽

Jin Shi ◽

Shu'an Wen ◽

Tingting Zhang ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Novel Mutation ◽

Multidrug Resistant ◽

23S Rrna ◽

Drug Resistant ◽

Content Type ◽

Extensively Drug Resistant ◽

Significant Difference ◽

Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

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Predominance of Beijing genotype in extensively drug resistant Mycobacterium tuberculosis isolates from a tertiary care hospital in New Delhi, India

International Journal of Mycobacteriology ◽

10.1016/j.ijmyco.2013.03.001 ◽

2013 ◽

Vol 2 (2) ◽

pp. 109-113 ◽

Cited By ~ 4

Author(s):

Jyoti Arora ◽

Manpreet Bhalla ◽

Zeeshan Sidiq ◽

Prabha Lal ◽

Digamber Behera ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Beijing Genotype ◽

New Delhi ◽

Care Hospital ◽

Drug Resistant ◽

Extensively Drug Resistant

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Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar

Acta Médica Portuguesa ◽

10.20344/amp.7882 ◽

2017 ◽

Vol 30 (3) ◽

pp. 175 ◽

Cited By ~ 2

Author(s):

Fernando Maltez ◽

Teresa Martins ◽

Diana Póvoas ◽

João Cabo ◽

Helena Peres ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Past History ◽

Multidrug Resistant ◽

Resistance Pattern ◽

Drug Resistant ◽

Beijing Family ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant ◽

Number Of Patients ◽

Drug Resistant Strains

Introduction: Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known.Material and Methods: Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains.Results: Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients).Discussion: Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa.Conclusion: Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

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